Patent application title: IMMUNOGENIC PROTEINS AND FRAGMENTS THEREOF FROM ALLERGENIC MITES

Inventors:
IPC8 Class: AC07K14435FI
USPC Class: 1 1
Class name:
Publication date: 2020-04-23
Patent application number: 20200123213

Abstract:

The invention relates to novel immunogenic polypeptides identified in house dust mites and storage mites, which have the potential to be used in allergy immunotherapy, for diagnostic purposes, eventually via production of antibodies binding the polypeptide or for characterising allergen extracts of house dust mites and storage mites.

Claims:

1. A polypeptide comprising or consisting of (a) an amino acid sequence selected from the group consisting of any one of SEQ ID NOs: 31, 291, 1-30, 32-44, 261-290, 292-332, or (b) an amino acid sequence consisting of at least or exactly 9 contiguous amino acid residues from the amino acid sequence of (a), or (c) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of (a), or (d) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of (b).

2. The polypeptide according to claim 1, wherein the sequence identity in option (c) is at least 65%, such as at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%.

3. The polypeptide according to any one of claim 1 or 2, wherein the polypeptide of option (c) has the same biological activity or functionality as the polypeptide of option (a) for example, the same enzymatic functionality, optionally the same, greater or less ability to elicit, stimulate or induce an immune response (e.g. in vitro T cell proliferation or T cell cytokine production, such as the cytokines, IL-4, IL-5, IL-13 and/or IL-10) in blood from a mite allergic individual; optionally the same, greater or less ability to induce immunological tolerance against mites, a mite allergen or the polypeptide of option (a) and/or to bind or interact with IgE, IgG or IgA antibodies raised against the polypeptide of option (a).

4. The polypeptide according to claim 1, wherein the at least or exactly 9 contiguous amino acid residues of option (b) or (d) constitute at least or exactly or at most 10, at least or exactly or at most 11, at least or exactly or at most 12, at least or exactly or at most 13, at least or exactly or at most 14, at least or exactly or at most 15, at least or exactly or at most 16, at least or exactly or at most 17, at least or exactly or at most 18, at least or exactly or at most 19, at least or exactly or at most 20, at least or exactly or at most 21, at least or exactly or at most 22, at least or exactly or at most 23, at least or exactly or at most 24, at least or exactly or at most 25, at least or exactly or at most 26, at least or exactly or at most 27 at least or exactly or at most 28, at least or exactly or at most 29, at least or exactly or at most 30, at least or exactly or at most 31, at least or exactly or at most 32, at least or exactly or at most 33, at least or exactly or at most 34, at least or exactly or at most 35, at least or exactly or at most 36, at least or exactly or at most 37, at least or exactly or at most 38, at least or exactly or at most 39, at least or exactly or at most 40, at least or exactly or at most 41, at least or exactly or at most 42, at least or exactly or at most 43, at least or exactly or at most 44, at least or exactly or at most 45, at least or exactly or at most 46, at least or exactly or at most 47, at least or exactly or at most 48, at least or exactly or at most 49, at least or exactly or at most 50, at least or exactly or at most 51, at least or exactly or at most 52, at least or exactly or at most 53, at least or exactly or at most 54, at least or exactly or at most 55, at least or exactly or at most 56, at least or exactly or at most 57, at least or exactly or at most 58, at least or exactly or at most 59, at least or exactly or at most 60, at least or exactly or at most 61, at least or exactly or at most 62, at least or exactly or at most 63, at least or exactly or at most 64, at least or exactly or at most 65, at least or exactly or at most 66, at least or exactly or at most 67, at least or exactly or at most 68, at least or exactly or at most 69, at least or exactly or at most 70, at least or exactly or at most 71, at least or exactly or at most 72, at least or exactly or at most 73, at least or exactly or at most 74, at least or exactly or at most 75, at least or exactly or at most 76, at least or exactly or at most 77, at least or exactly or at most 78, at least or exactly or at most 79, at least or exactly or at most 80, at least or exactly or at most 81, at least or exactly or at most 82, at least or exactly or at most 83, at least or exactly or at most 84, at least or exactly or at most 85, at least or exactly or at most 86, at least or exactly or at most 87, at least or exactly or at most 88, at least or exactly or at most 89, at least or exactly or at most 90, at least or exactly or at most 91, at least or exactly or at most 92, at least or exactly or at most 93, at least or exactly or at most 94, at least or exactly or at most 95, at least or exactly or at most 96, at least or exactly or at most 97, at least or exactly or at most 98, at least or exactly or at most 99, at least or exactly or at most 100, at least or exactly or at most 101, at least or exactly or at most 102, at least or exactly or at most 103, at least or exactly or at most 104, at least or exactly or at most 105, at least or exactly or at most 106, at least or exactly or at most 107, at least or exactly or at most 108, at least or exactly or at most 109, at least or exactly or at most 110, at least or exactly or at most 111, at least or exactly or at most 112, at least or exactly or at most 113, at least or exactly or at most 114, at least or exactly or at most 115, at least or exactly or at most 116, at least or exactly or at most 117, at least or exactly or at most 118, at least or exactly or at most 119, at least or exactly or at most 120, at least or exactly or at most 121, at least or exactly or at most 122, at least or exactly or at most 123, or at least or exactly or at most 124 amino acid residues.

5. The polypeptide according to any one of claim 1 or 4, wherein the contiguous amino acid residues of option (b) or (d) commence at amino acid residue 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, or 117 in any one of SEQ ID NOs: 1-44 and 261-332; or at amino acid residue 118, 119, 120, 121, or 122 in any one of SEQ ID NOs: 1-44, 261-304, 306-318, and 320-332; or at amino acid residue 123 or 124 in any one of SEQ ID NOs: 2-44, 262-304, 306-318, and 320-332; or at amino acid residue 125 or 126 in any one of SEQ ID NOs: 4-44, 264-304, 306-318, and 320-332; or at amino acid residue 127, 128, or 129 in any one of SEQ ID NOs: 5-44, 265-304, 306-318, and 320-332; or at amino acid residue 130, 131, 132, 133, 134, 135, 136, 135, 136, 137, 138, 139, 140, 141, 142 in any one of SEQ ID NOs: 5-44, 265-304, 306-314, 316-318, 320-328, and 330-332; or at amino acid residue, 143 or 144 in any one of SEQ ID NOs: 5-44, 265-304, 306-313, 316-318, 320-327, and 330-332; or at amino acid residue 145 and 146 in any one of SEQ ID NOs: 7-44, 267-304, 306-313, 316-318, 320-327, and 330-332; or at amino acid residue 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, or 163 in any one of SEQ ID NOs: 9-44, 269-304, 306-313, 316-318, 320-327, and 330-332; or at amino acid residue 164 in any one of SEQ ID NOs: 10-44, 270-304, 306-313, 316-318, 320-327, and 330-332; or at amino acid residue 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178 in any one of SEQ ID NOs: 11-44, 271-304, 306-313, 316-318, 320-327, and 330-332; or at amino acid residue 179 or 180 in any one of SEQ ID NOs: 11-44 and 271-304, 306-313, 316-317, 320-327, and 330-331; or at amino acid residue 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, or 214 in any one of SEQ ID NOs: 13-44, 273-304, 306-313, 316-317, 320-327, and 330-331; or at amino acid residue 215, 216, 217, 218, 219, or 220 in any one of SEQ ID NOs: in any one of SEQ ID NOs: 15-44, 275-304, 306-313, 316-317, 320-327, and 330-331; or at amino acid residue 221 in any one of SEQ ID NOs: 17-44 and 275-304; or at amino acid residue 222, 223, or 224 in any one of SEQ ID NOs: 17, 19-44, 277, 279-304, 306-313, 316-317, 320-327, and 330-331; or at amino acid residue 225 in any one of SEQ ID NOs: 17, 19-44, 277, 279-304, 306-313, 317, 320-327, and 331; or at amino acid residue 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, or 244 in any one of SEQ ID NOs: 19-44, 279-304, 306-313, 317, 320-327, and 331; or at amino acid residue 245 in any one of SEQ ID NOs: 20-44, 280-304, 306-313, and 320-327; or at amino acid residue 246, 247, 248, 249, 250, 251, or 252 in any one of SEQ ID NOs: 21-44 and 281-304, 306-313, and 320-327; or at amino acid residue 253 in any one of SEQ ID NOs: 21-44, 281-304, 306-312, and 320-326; or at amino acid residue 254 in any one of SEQ ID NOs: 22-44 and 282-304; or at amino acid residue 255, 256, 257, 258, 259, 260, 261, or 262 in any one of SEQ ID NOs: 23-44, 283-304, 306-312, and 320-326; or at amino acid residue 263 in any one of SEQ ID NOs: in any one of SEQ ID NOs: 24-44, 284-304, 306-312, and 320-326; or at amino acid residue 264, 265, 266, or 267 in any one of SEQ ID NOs: 25-44, 285-304, 306-312, and 320-326; or at amino acid residue 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301 in any one of SEQ ID NOs: 26-44, 286-304, 306-312, and 320-326; or at amino acid residue 302 in any one of SEQ ID NOs: 26-44, 286-304, 306-311, and 320-325; or at amino acid residue, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, or 313 in any one of SEQ ID NOs: 27-44, 287-304, 306-311, and 320-325; or at amino acid residue 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, or 324 in any one of SEQ ID NOs: 28-44, 288-304, 306-311, and 320-325; or at amino acid residue 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, or 353 in any one of SEQ ID NOs: 30-44, 290-304, 306-311, and 320-325; or at amino acid residue 354 in any one of SEQ ID NOs: 31-44 291-304, 306-311, and 320-325; or at amino acid residue 355 in any one of SEQ ID NOs: 32-44 292-304, 306-311, and 320-325; or at amino acid residue 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, or 421 in any one of SEQ ID NOs: 32-44, 292-304, 307-311, and 321-325; or at amino acid residue 422, 423, 424, 425, or 426 in any one of SEQ ID NOs: 33-44, 293-304, 307-311, and 321-325; or at amino acid residue 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451 in any one of SEQ ID NOs: 34-44, 294-304, 307-311, and 321-325; or at amino acid residue 452, 453, or 454 in any one of SEQ ID NOs: 34-44, 294-304, 307-310, and 321-324; or at amino acid residue 455 in any one of SEQ ID NOs: 36-44, 296-304, 307-310, and 321-324; or at amino acid residue 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, or 466 in any one of SEQ ID NOs: 37-44, 297-304, 307-310, and 321-324; or at amino acid residue 467, 468, 469, 470, 471, 472, 473, or 474 in any one of SEQ ID NOs: 38-44, 298-304, 307-310, and 321-324; or at amino acid residue 475, 476, 477, 478, 479, 480, 481, 482, or 483 in any one of SEQ ID NOs: 38-44, 298-304, 307, 308, 310, 321, 323, and 324; or at amino acid residue 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, or 501 in any one of SEQ ID NOs: 38-44, 298-304, 307, 308, 321, and 323; or at amino acid residue 502, 503, 504, 505, 506, 507, 508, 509, 510, or 511 in any one of SEQ ID NOs: 39-44, 299-304, 307, 308, 321, and 323; or at amino acid residue 512 in any one of SEQ ID NOs: 39, 41-44, 299, 301-304, 307, 308, 321, and 323; or at amino acid residue 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868, 869, 870, 871, 872, 873, 874, 875, 876, or 877 in any one of SEQ ID NOs: 41-44 301-304, 307, 308, 321, and 323; or at amino acid residue 878 or 879 in any one of SEQ ID NOs: 41, 43, 44, 301, 303, 304, 307, 308, 321, and 323; or at amino acid residue 880 or 881 in any one of SEQ ID NOs: 43, 44, 303, 304, 307, 308, 321, and 323; or at amino acid residue, 882, 883, 884, 885, 886, 887, 888, 889, 890, 891, 892, 893, 894, 895, 896, 897, 898, 899, 900, 901, 902, 903, 904, 905, 906, 907, 908, 909, 910, 911, 912, 913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924, 925, 926, 927, 928, 929, 930, 931, 932, 933, 934, 935, 936, 937, 938, 939, 940, 941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954, 955, 956, 957, 958, 959, 960, 961, 962, 963, 964, 965 in any one of SEQ ID NOs: 43, 44, 303, 304, 307, and 321; or at amino acid residue, 966 or 967 in any one of SEQ ID NOs: 43, 44, 303, and 304; or at amino acid residue 968, 969, 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, or 982 in SEQ ID NO: 44 or 304; with the proviso that the number, N, of the commencing amino residue satisfies the formula N.ltoreq.L-n+1, where L is the number of amino acid residues in the sequence among SEQ ID NOs: 1-44 and 261-332 from which the commencing residue is selected, and n is the number of consecutive amino acid residues.

6. The polypeptide according to any one of claims 1, 4 and 5, wherein the sequence identity in option (d) is at least 60%, such as at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%.

7. The polypeptide according to any one of claims 1, 4-6, wherein the polypeptide of option (d) may have the same biological activity or functionality as the polypeptide of option (b), for example, it may have the same enzymatic functionality, it may have the same, greater or less ability to elicit, stimulate or induce an immune response (e.g. in vitro T cell proliferation or T cell cytokine production (for example the cytokines, IL-4, IL-5, IL-13 and/or IL-10) in blood of a mite allergic individual; to induce immunological tolerance against mites, mite allergens or the polypeptide of option (b); and/or to bind or interact with IgE, IgG or IgA antibodies raised against the polypeptide of option (b).

8. The polypeptide according to any one of claims 1, 4-7, wherein the polypeptide of option (b) and (d) has a length of 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acid residues.

9. The polypeptide according to claim 8, wherein the polypeptide of option (d) has greater or less ability to bind a Class HLA II allele or a group of Class HLA II alleles than the parent polypeptide of option (b), for example, the polypeptide of option (d) may bind to at least 70%, such as at least 75%, 80%, 85%, 90% or 95% of the Class HLA II alleles that the parent polypeptide of option (b) binds to.

10. The polypeptide according to any one of claims 1, 4-9, wherein the consecutive amino acids of option (b) and (d) comprise a T cell epitope, optionally a Th2 cell epitope.

11. The polypeptide according to any one of the preceding claims, which comprises or consists of an amino acid sequence consisting of a) 9, 10, 11, 12, 13, 14 or 15 consecutive amino acid residues from a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260 and any one of SEQ ID NOs: 45, 61, 63, 80, 100, 113, 147, 154, 170, 172, 191, 215, 225, 226, 248, and 260, wherein any cysteine residue is/are substituted with a serine residue, an alanine residue or a 2-aminobutyric acid residue, or b) a variant of 9 consecutive amino acid residues from a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260, wherein 1 or 2 or 3 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent polypeptide sequence, or c) a variant of 10 consecutive amino acid residues from a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260, wherein 1 or 2 or 3 or 4 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent polypeptide sequence, or d) a variant of 11 consecutive amino acid residues from a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260, wherein 1 or 2 or 3 or 4 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent polypeptide sequence, or e) a variant of 12 consecutive amino acid residues from a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260, wherein 1 or 2 or 3 or 4 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent polypeptide sequence, or f) a variant of 13 consecutive amino acid residues from a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260, wherein 1, 2, 3, 4, or 5 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent polypeptide sequence, or g) a variant of 14 consecutive amino acid residues from a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260, wherein 1, 2, 3, 4, or 5 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent polypeptide sequence h) a variant of a parent polypeptide sequence selected from any one of SEQ ID NOs: 45-260, wherein 1, 2, 3, 4, 5, or 6 amino acids are substituted with a different amino acid in the variant relative to the parent polypeptide sequence.

12. The polypeptide according to claim 11, wherein the parent polypeptide sequence commences at residue 1, 2, 3, 4, 5, 6, or 7 in any one of SEQ ID NOs: 45-260 when the peptide is 9 amino acids in length, or residue 1, 2, 3, 4, 5, or 6 in any one of SEQ ID NOs: 45-260 when the peptide is 10 amino acids in length, or residue 1, 2, 3, 3, 4, or 5 in any one of SEQ ID NOs: 45-260 when the peptide is 11 amino acids in length, or residue 1, 2, 3, or 4 in any one of SEQ ID NOs: 45-260 when the peptide is 12 amino acids in length, or residue 1, 2, or 3 in any one of SEQ ID NOs: 45-260 when the peptide is 13 amino acids in length, or residue 1 or 2 in any one of SEQ ID NOs: 45-260 when the peptide is 14 amino acids in length.

13. The polypeptide according to any one of claims 11 and 12, wherein the polypeptide of option a) to h) comprises a T cell epitope, optionally a Th2 cell epitope.

14. The polypeptide according to any one of claims 11-13, which comprises any one of SEQ ID NOs: 45-260.

15. The polypeptide according to any one of claims 11-14, wherein the polypeptide has a length of 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acid residues.

16. The polypeptide according to any one of the preceding claims, which is able to cross-react with any one of SEQ ID NOs: 1-260 when tested in a T-cell proliferation assay employing T cells from a patient allergic to the mites or the protein allergens.

17. The polypeptide according to any one of the preceding claims, which consists of an amino acid sequence identical with the amino acid sequence of a proteolytic fragment of a protein consisting of an amino acid sequence selected from any one of SEQ ID NOs: 1-44, and 261-332, preferably from any one of SEQ ID NOs: 1-44 and 305-318.

18. The polypeptide according to claim 17, wherein the proteolytic fragment is a tryptic or chymotryptic fragment.

19. The polypeptide according to claim 17 or 18, which includes a mass modifying label.

20. The polypeptide according to any one of the preceding claims, which comprises at least one of the following modifications: a)N-terminal acetylation or methylation b) C terminal amidation c)C-terminal amination d) addition of one to three charged amino acid residues selected from any one of lysine (K), arginine (R), aspartic acid (D), and glutamic acid (E) in the N-terminal or C-terminal e) replacement of one or more hydrogen(s) on the side chain amines of arginine and/or lysine with a methylene group f) glycosylation, and g) phosphorylation.

21. A composition, such as a pharmaceutical composition, comprising one or more of the polypeptides according to any one of the preceding claims.

22. The pharmaceutical composition according to claim 21, further comprising a pharmaceutically acceptable carrier, excipient, and/or adjuvant, optionally sterile.

23. The pharmaceutical composition according to claim 21 or 22 formulated as a vaccine for parenteral administration.

24. The pharmaceutical composition according to any one of claims 21-23, wherein the pharmaceutical composition is a powder, optionally formulated to be re-dissolved before use.

25. A method of treating allergy in a patient, where signs and/or symptoms of said allergy are elicited in the patient by exposure to house dust mites or storage mites and/or exposure to at least one protein allergen present in house dust mites or storage mites, the method comprising administering, to the patient, a therapeutically effective amount of a polypeptide according to any one of claims 1-20 or the composition according to any one of claims 21-24.

26. The method according to claim 25, wherein exposure of the patient to the polypeptide does not elicit signs or symptoms of allergy in the patient.

27. The method according to claim 25 or 26, wherein exposure of the patient to one or more protein(s) having an amino acid sequence consisting of or comprising an amino acid sequence selected from SEQ ID NOs: 1-44 or 261-304 does not elicit signs of allergy (i.e. IgE-mediated allergy) in the patient.

28. The method according to any one of claims 25-27, wherein treating the allergy comprises or consists of relieving or reducing an immune response triggered by exposure to the mites or the protein allergen.

29. The method according to any one of claims 25-28, wherein treating the allergy comprises or consists of relieving one or more symptoms of an immune response triggered by exposure to the mites or the protein allergen.

30. The method according to any one of claims 25-29, wherein treating the allergy consists of or comprises inducing immunological tolerance against the mites or the protein allergen.

31. The method according to any one of claims 25-30, wherein treating the allergy comprises or consists of relieving one or more symptom(s) associated with allergic rhinitis and/or allergic conjunctivitis and/or allergic asthma and/or allergic eczema (e.g. atopic dermatitis).

32. The method according to any one of claims 25-31, wherein treating the allergy comprises or consists of relieving one or more signs or symptoms associated with allergic rhinitis, such as reducing the intensity of itchy nose and/or reducing the number of sneezes within a given period (e.g. daily, weekly, monthly) and/or reducing the intensity of blocked nose (congestion) and/or reducing the amount of nasal fluid and/or reducing the eosinophilic count in nasal fluid and/or reducing specific IgE antibody level (titre) in nasal fluid or in serum and/or reducing basophil histamine release in blood.

33. The method according to any one of claims 25-32, wherein treating the allergy comprises or consists of relieving one or more signs or symptoms associated with allergic conjunctivitis, such as reducing the intensity of itchy eyes, redness in the white of the eyes and/or watery eyes; and/or reducing the eosinophilic count in conjunctival tissue scrapings; and/or reducing specific IgE antibody level (titer) in conjunctival tissue scrapings or in serum; and/or reducing basophil histamine release in blood.

34. The method according to any one of claims 25-33, wherein treating the allergy comprises or consists of relieving one or more signs or symptoms associated with allergic asthma, such as reducing the intensity and/or number of coughs within a given period (e.g. daily, weekly, monthly); and/or reducing the intensity of wheezes; and/or improving being short of breath; and/or improving lung function; and/or reducing specific IgE antibody level (titre) in lung fluid or in serum; and/or reducing basophil histamine release in blood.

35. The method according to any one of claims 25-34, wherein treating the allergy comprises or consists of relieving one or more signs or symptoms associated with atopic dermatitis, such as reducing itch intensity of the skin; and/or reducing eczema score; and/or reducing number of (peripheral) blood eosinophils.

36. The method according to any one of claims 25-35, comprising or consisting of reducing the patient's need for concomitant treatment with corticosteroids or H1 antihistamines to reduce, relieve or suppress one or more symptoms of an immune response associated with the allergy.

37. The method according to claim 36, wherein the immune response is clinically presented as atopic dermatitis, urticaria, contact dermatitis, allergic conjunctivitis, allergic rhinitis, allergic asthma, anaphylaxis, and/or hay fever.

38. The method according to claim 36 or 37, wherein the method decreases, reduces, suppresses or inhibits atopic dermatitis, urticaria, contact dermatitis, allergic conjunctivitis, allergic rhinitis, allergic asthma, anaphylaxis, and/or hay fever.

39. The method according to any one of claims 25-38, comprising inducing or increasing an IgG antibody response in the patient to a protein allergen of the mites and/or decreasing an IgE antibody response in the patient to a protein allergen of the mites and/or decreasing a T cell response in the patient against a protein allergen of the mites.

40. The method according to any one of claims 25-39, wherein the patient is sensitized to at least one protein allergen of the mites.

41. The method according to any one of claims 25-40, wherein the mites are house dust mites of the genus Dermatophagoides (for example selected from the group consisting of Dermatophagoides pteronyssinus, Dermatophagoides farinae) or of the genus Euroglyphus (for example Euroglyphus maynei), or wherein the mites are storage mites of the genus Glycyphagus, Lepidoglyphus, Tyrophagus, or Blomia (for example Glycyphagus domesticus, Lepidoglyphus destructor, Tyrophagus putrescentiae, or Blomia tropicalis).

42. The method according to any one of claims 25-41, wherein the protein allergen is selected from one or more protein allergens in the groups consisting of a group 1 allergen of mites (for example a group 1 allergen of a house dust mite (e.g. Der p 1, Der f 1, or Eur m 1, or a group 1 allergen of a storage mite, e.g. Gly d 1, Lep d 1, Typ p 1 and Blo t 1) and a group 2 allergen of mites (for example a group 2 allergen of a house dust mite, e.g. Der p 2, Der f 2 and Eur m 2, and a group 2 allergen of a storage mite, e.g. Gly d 2, Lep d 2, Typ p 2 and Blo t 2).

43. The method according to any one of claims 25-42, wherein the signs or symptoms of allergy not elicited by the polypeptide are one or more signs or symptoms selected from the group consisting of: the presence in the patient of specific IgE antibodies that binds to the immunogen; a positive skin prick test with the polypeptide; and the signs or symptoms defined in any one of claims 31-35.

44. An in vitro method of determining whether T cells of a subject are responsive to one or more of the polypeptides according to any one of claims 1-20 and/or the composition according to any one of claims 21-24, comprising a step of contacting T cells obtained from the subject with said polypeptide(s) or composition and detecting whether the T cells are stimulated.

45. An in vitro method of diagnosing a subject for sensitization to (allergy to) house dust mites or storage mites, comprising a step of contacting T cells obtained from the subject with one or more of the polypeptides according to any one of claims 1-20 and/or the composition according to any one of claims 21-24 and detecting whether the T cells are stimulated.

46. An in vitro method for determining whether a subject has, or is at risk of developing, an allergy to house dust mites or storage mites, comprising a step of contacting T cells obtained from the subject with one or more of the polypeptides according to any one of claims 1-20 and/or the composition according to any one of claims 21-24 and detecting whether the T cells are stimulated.

47. A diagnostic kit comprising one or more of the polypeptides according to any one of claims 1-20 and/or the composition according to any one of claims 21-24.

48. An isolated nucleic acid fragment, which comprises i) a nucleotide sequence encoding a polypeptide according to any one of claims 1-20, or ii) a nucleotide sequence complementary to the nucleotide sequence in i).

49. The nucleic acid fragment according to claim 48, which is a DNA or an RNA fragment.

50. A vector comprising the nucleic acid fragment according to claim 48, such as a cloning vector or an expression vector.

51. The vector according to claim 50, which comprises in operable linkage and in the 5'-3' direction, an expression control region comprising an enhancer/promoter for driving expression of the nucleic acid fragment defined in claim 48-i), optionally a signal peptide coding sequence, a nucleotide sequence defined in claim 48-i), and optionally a terminator.

52. The vector according to claim 51, wherein the expression control region drives expression in prokaryotic cell such as a bacterium, e.g. in E. coli.

53. The vector according to claim any one of claims 50-52, which is capable of autonomous replication.

54. The vector according to any one of claims 50-53, which is capable of being integrated into the genome of a host cell.

55. The vector according to any one of claims 50-54, which is selected from the group consisting of a virus, such as an attenuated virus, a bacteriophage, a plasmid, a minichromosome, and a cosmid.

56. A cell which is transformed to carry the vector according to any one of claims 50-55.

57. The transformed cell according to claim 56, which is capable of replicating the nucleic acid fragment defined in claim 48-i) and/or which is capable of expressing the nucleic acid fragment defined in claim 48-i).

58. The transformed cell according to claim 56 or 57, which is selected from a prokaryotic cell and a eukaryotic cell.

59. The transformed cell according to any one of claims 56-58, which is a bacterial cell selected from the group consisting of Escherichia (such as E. coli.), Bacillus (e.g. Bacillus subtilis), Salmonella, and Mycobacterium, preferably non-pathogenic, e.g. M. bovis BCG.

60. The transformed cell according to any one of claims 56-59, which is stably transformed by having the nucleic acid defined in claim 48-i) stably integrated into its genome.

61. The transformed cell according to any one of claims 56-60, which secretes or carries on its surface the polypeptide according to any one of claims 1-20.

62. The transformed cell according to claim 61, wherein the cell is a bacterium and secretion is into the periplasmic space.

63. A cell line derived from the transformed cell according to any one of claims 56-62.

64. A method for the preparation of the polypeptide according to any one of claims 1-20, comprising culturing a transformed cell according to any of claims 56-62 or the cell line according to claim 63 under conditions that facilitate that the transformed cell expresses the nucleic acid fragment according to claim 48-i) and subsequently recovering said polypeptide, or preparing said polypeptide by means of solid or liquid phase peptide synthesis.

65. An isolated polyclonal antibody, which has been raised against the polypeptide according to any one of claims 1-20.

66. A monoclonal antibody or a fragment or analogue thereof, which specifically binds the polypeptide according to any one of claims 1-20 wherein said fragment or analogue comprises at least the variable regions of the antigen binding site of said monoclonal antibody.

67. A method for qualitative or quantitative determination of the presence in a sample of the polypeptide according to any one of claims 1-20, the method comprising any one of the following approaches: contacting the sample with an antibody according to any one of claim 65 or 66 and detecting specific binding of material in said sample to said antibody, contacting the sample with a system comprising a solid phase with an antibody according to claim 65 or 66 coupled thereto and comprising a labelled polypeptide according to any one of claims 1-20, where said labelled polypeptide specifically binds said antibody, and gauging the degree of competition exerted by material in the sample on the binding between said labelled polypeptide and said antibody, contacting the sample with a system comprising 1) a solid phase with a polypeptide according to any one of claims 1-20 coupled thereto and comprising 2) a labelled antibody according to claim 65 or 66, where said polypeptide specifically binds said labelled antibody, and gauging the degree of competition exerted by material in the sample on the binding between said polypeptide and said antibody, subjecting polypeptide material from the sample to proteolytic treatment and subjecting the thus obtained material to quantitative MS, optionally using at least one polypeptide according to any one of claims 17-19 as standard calibration peptide.

Description:

FIELD OF THE INVENTION

[0001] The present invention relates to the field of medicine, in particular allergy immunotherapy against mite allergy. The present invention deals with a group of immunogenic polypeptides with low IgE antibody reactivity but considerable T cell reactivity in a mite allergic population.

[0002] The immunogenic polypeptides are conserved across important species of house dust mites as well as storage mites, and may be usable in the field of allergy immunotherapy against mite allergy.

BACKGROUND OF THE INVENTION

[0003] House dust mites of the genus Dermatophagoides are one of the most frequent indoor allergen sources worldwide and are potent inducers of perennial asthma and rhinitis. Several groups of allergens from the most important species (Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f)) are reported (http\www.allergen.org). The group 1 allergens (e.g. Der p 1 and Der f 1) and the group 2 allergens (e.g. Der p 2 and Der f 2) are considered the clinically most important allergens among house dust mites with IgE binding frequencies of more than 80 percent. Other known allergens from the genus Dermatophagoides have variable levels of IgE antibody titers, e.g. Der p 4, 5, 7, 8, 10, 11, 13-15, 18, 20, 21 and 23. In some tropical and subtropical regions of the world, the clinically most important mite allergens may be from both house dust mites and storage mites of which storage mites of the genus Blomia (e.g. of the species Blomia tropicalis) may be more clinically important than of the genus Dermatophagoides. While the major allergens of the species Der p and Der f are highly cross-reactive and have sequence identity of above 80-85%, the sequence identity to the corresponding allergens in storage mite species are much lower (below 40-50%).

[0004] Allergen-specific immunotherapy (SIT) represents a causative and disease-modifying approach with long-lasting effects with the efficacy of reducing the symptom burden and concomitant medication use. SIT is based on the administration of increasing doses of the disease-eliciting allergens into sensitized subjects in order to achieve a state of clinical tolerance to subsequent exposure. Conventionally, SIT includes subcutaneous injection (SCIT) or sublingual administration (SLIT) of a pharmaceutical formulation of an allergen extract of the disease-eliciting allergen source, e.g. an allergen extract of house dust mite bodies and fecal particles. Conventional SIT may induce severe side-effects in allergic patients, e.g. anaphylaxis, though SLIT has been proven to have a superior safety profile to SCIT. However, the risk of inducing anaphylaxis is still not negligible because the allergen extracts contains considerable amounts of IgE-reactive allergens. This may limit the broad applicability of this treatment approach.

[0005] Current SIT products on the market target either house dust mite allergy or storage mite allergy. Thus, patients with dual sensitization to both house dust mite species and storage mite species may not be well treated by current SIT products.

[0006] Accordingly, an unmet need exists in the art for allergy immunotherapeutic products with high safety profile and efficacy to both house dust mites and optionally storage mites.

OBJECT OF THE INVENTION

[0007] It is an object of embodiments of the invention to provide proteins and fragments thereof with low or absent IgE reactivity, but T cell reactivity in a high fraction of a mite allergic population and which have sequences with high sequence identity to proteins present in house dust mites and optionally also storage mites.

SUMMARY OF THE INVENTION

[0008] The present inventors have identified a number of proteins present in house dust mites. The proteins share the feature of being immunogenic in the sense that they, at least, elicit T cell responses in a high fraction of a mite allergic population, while only a low or insignificant fraction of the same population has raised an IgE antibody immune response against these proteins as such. This renders the use of these proteins and optionally peptides thereof relevant for treatment of allergy, optionally by exploitation of the bystander suppression effect, e.g. as disclosed in WO 2012/049310: effective immunization of a patient to obtain a tolerogenic immune response with a first immunogenic protein, preferably a protein the patient has not raised IgE antibodies against, which is present in a material (e.g. an allergen-source material) which causes allergy in the patient due to the presence of at least one protein allergen (e.g. a protein to which the patient has raised IgE antibodies), followed by later exposure of the patient to both the first protein and the allergen-source material has the consequence that the tolerogenic immune response induced by the first protein suppresses the undesired allergic immune response induced by the protein allergen. So, somewhat paradoxically, immunization with a protein immunogen different from the protein allergen can reduce a later immune response against a protein allergen to which the patient is exposed, provided that this later exposure is accompanied by exposure to the protein immunogen.

[0009] Thus, in a first aspect the present invention relates to a polypeptide comprising or consisting of

[0010] (a) an amino acid sequence selected from the group consisting of any one of SEQ ID NOs: 1-44 and 261-332, or

[0011] (b) an amino acid sequence consisting of at least or exactly 9 contiguous amino acid residues from the amino acid sequence of (a), or

[0012] (c) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of (a), or

[0013] (d) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of (b).

[0014] In a related second aspect, the present invention relates to a composition, such as a pharmaceutical composition, comprising one or more of the polypeptides of the first aspect of the invention.

[0015] A third aspect of the invention relates to a method of treating allergy (i.e. IgE-mediated allergy) in a patient, where signs and/or symptoms of said allergy are elicited in the patient by exposure to house dust mites or storage mites and/or exposure to at least one protein allergen present in house dust mites or storage mites, the method comprising administering, to the patient, a therapeutically effective amount of a polypeptide of the first aspect of the invention or a composition of the second aspect of the invention.

[0016] Consequently, in related aspects, the invention relates to the polypeptides of the first aspect and/or the composition of the second aspect for use as a pharmaceutical, in particular for use in a method of the third aspect of the invention. Likewise, in related aspects the invention relates to use of a polypeptide of the first aspect of the invention or the composition of the second aspect of the invention in a method of the third aspect of the invention. And, in related aspects, the invention relates to use of the polypeptides of the first aspect of the invention in the preparation of a pharmaceutical composition for use in a method of the second aspect of the invention.

[0017] A fourth aspect of the invention relates to an in vitro method of determining whether T cells of a subject are responsive to one or more of the polypeptides of the first aspect of the invention and/or the composition of the second aspect of the invention, comprising a step of contacting T cells obtained from the subject with said one or more polypeptides of the first aspect of the invention and/or the composition of the second aspect of the invention and detecting whether the T cells are stimulated.

[0018] A fifth aspect of the invention relates to an in vitro method of diagnosing a subject for sensitization or allergy to house dust mites or storage mites, comprising contacting T cells obtained from the subject with one or more of the polypeptides of the first aspect of the invention and/or the composition of the second aspect of the invention and determining whether the T cells are stimulated.

[0019] A sixth aspect of the invention relates to an in vitro method for determining whether a subject has, or is at risk of developing, an allergy to house dust mites or storage mites, comprising contacting T cells obtained from the subject with one or more of the polypeptides of the first aspect of the invention and/or the composition of the second aspect of the invention and determining whether the T cells are stimulated.

[0020] A seventh aspect relates to an in vitro method of diagnosing a subject for allergy or sensitivity to house dust mites or storage mites, comprising determining the presence of specific IgE against one or more of the polypeptides of the first aspect of the invention and/or the composition of the second aspect of the invention in a biological sample (e.g. serum) obtained from the subject.

[0021] An eighth aspect of the invention relates to a diagnostic kit comprising one or more of the polypeptides of the first aspect of the invention and/or the composition of the second aspect of the invention.

[0022] A ninth aspect of the invention relates to a nucleic acid fragment, which encodes a polypeptide of the first aspect of the invention.

[0023] A tenth aspect of the invention relates to a vector comprising a nucleic acid fragment of the ninth aspect of the invention.

[0024] An eleventh aspect of the invention relates to a transformed cell carrying a nucleic acid fragment of the ninth aspect of the invention or a vector of the tenth aspect of the invention.

[0025] Included in this aspect is also a cell line derived from the transformed cell.

[0026] A twelfth aspect of the invention relates to a method of preparing a polypeptide of the first aspect of the invention, the method comprising culturing a transformed cell of the tenth aspect of the invention under conditions that facilitate expression of the nucleic acid fragment of the ninth aspect, and subsequently recovering the expression product (a polypeptide of the second aspect of the invention) from the culture medium.

[0027] A thirteenth aspect of the invention relates to an antibody (polyclonal, monoclonal) or an antibody fragment or analogue that specifically binds the polypeptide of the first aspect of the invention.

[0028] Finally, a fourteenth aspect relates to a method for qualitative or quantitative determination of the presence in a sample of the polypeptide of the first aspect, the method comprising any one of the following approaches:

[0029] contacting the sample with an antibody of the thirteenth aspect and detecting specific binding of material in said sample to said antibody,

[0030] contacting the sample with a system comprising a solid phase with an antibody of the thirteenth aspect coupled thereto and comprising a labelled polypeptide of the first aspect, where said labelled polypeptide specifically binds said antibody, and gauging the degree of competition exerted by material in the sample on the binding between said labelled polypeptide and said antibody,

[0031] contacting the sample with a system comprising 1) a solid phase with a polypeptide of the first aspect coupled thereto and comprising 2) a labelled antibody of the thirteenth aspect, where said polypeptide specifically binds said labelled antibody, and gauging the degree of competition exerted by material in the sample on the binding between said polypeptide and said antibody,

[0032] subjecting polypeptide material from the sample to proteolytic treatment and subjecting the thus obtained material to quantitative MS, optionally using at least one polypeptide described herein as useful as a standard calibration peptide.

DETAILED DISCLOSURE OF THE INVENTION

Definitions

[0033] The term "antigen" is an agent that is recognized (i.e. bound by) an antibody and/or a T cell receptor. The latter is normally only possible when the antigen is presented in the context of an MHC Class I or II molecule and after being processed by an antigen presenting cell such as a macrophage or a dendritic cell. This means that relatively large polypeptides may be antigens even though they do not directly bind a T cell receptor but since shorter peptides that are products of antigen presenting cell-processing are recognized by T cell receptors, such proteins are nevertheless termed "antigens".

[0034] An "immunogen" is a type of antigen, which is capable of eliciting a specific adaptive immune response that targets the antigen, i.e. immunogens are able to induce the production by the animal body of the antibodies and T cells that recognize antigens. This is in contrast to "haptens", which denote antigens that are not themselves capable of inducing an immune response but which are capable of being recognized by antibodies and/or T-cell receptors.

[0035] Of particular interest are "protein antigens", "protein immunogens", "polypeptide antigens", "polypeptide immunogens", "peptide antigens", and "peptide immunogens", which are each characterized by comprising or consisting of a protein, polypeptide or peptide, which in itself is an antigen or immunogen.

[0036] The terms "protein", "polypeptide", "oligopeptide", and "peptide" are used interchangeably herein if no other characteristics are used to describe these molecules in terms of molecule size or length: where a polypeptide and protein typically is of a larger size (e.g. >100 amino acid residues), an oligopeptide has between 10 and 100 amino acid residues, and a peptide is an even shorter molecule, the present description and claims will as a rule indicate the relevant length of the proteins, polypeptides, oligopeptides and peptides disclosed herein.

[0037] These molecules are characterized by being constituted of multiple amino acid residues linked via peptide bonds. Typically all the amino acid residues (except for glycine, which is achiral) are in the L-form (since this allows for processing of the polypeptides by antigen presenting cells), but the presence of D-amino acid residues is not excluded.

[0038] A "protein" is also meant to designate a biomolecule comprising or consisting of at least one polypeptide, oligopeptide, or peptide, but which optionally may include other molecular entities, such as prosthetic groups, sugars, lipids, and various other derivatizations of the side groups in the amino acid chain(s). For example, the human adult protein hemoglobin is composed of 4 (2+2) polypeptides (2 identical a chains and 2 identical 13 chains), which are each tightly associated to a heme group (a prostethetic group).

[0039] As used herein an "epitope" refers to a region or part of an antigen, such as a poly(peptide) or protein disclosed herein, that elicits an immune response when administered to a subject.

[0040] An epitope may be a T cell epitope, i.e., an epitope that elicits, stimulates, induces, promotes, increases or enhances a T cell activity, function or response; for example a Th2 cell epitope. Any peptide or combination of peptides of interest can be analyzed to determine whether they include at least one T cell epitope using any number of assays known in the art (e.g. T cell proliferation assays, lymphokine secretion assays, T cell non-responsiveness studies, etc.).

[0041] The term "allergen" refers to an antigen which elicits, induces, stimulates, or enhances an immune response, e.g. Th.sub.2-immune response, by a cell of the immune system of an exposed animal (e.g., human). An antigen is an allergen when the specific immune response is the development of enhanced sensitivity or a hypersensitivity to the antigen, but the antigen itself is not typically innately harmful. An allergen is therefore a particular type of antigen that can cause development of enhanced or increased sensitivity or hypersensitivity in a subject. For example, an allergen can elicit production of IgE antibodies and histamine release from mast cells or basophil cells in predisposed subjects.

[0042] If no other meaning is given specifically, the term "T cell response" refers to induction of cytokines or proliferation of a T cell in response to an immunogen. It may be determined as explained in Example 2. It may in some instances be referred to simply as a "response" to an immunogen, such as a peptide, polypeptide or a protein.

[0043] The term "allergic response" is intended to refer to the hypersensitive immune reaction to a normally innocuous environmental substance known as an allergen. The most common mechanism of allergic reactions is the binding of IgE to the FcERI on the surface of mast cells and basophils, which in turn causes asthma, hay fever and other common allergic reactions due to release of cytokines, notably histamine.

[0044] The term "identity" and "identical" and grammatical variations thereof, as used herein, mean that two or more referenced entities are the same (e.g., amino acid sequences). Thus, where two proteins, polypeptides or peptides are identical, they have the same amino acid sequence. The identity can be over a defined area, e.g. over at least 12, 13, 14, 15, 16, 17, 18, 19, 20, or more contiguous amino acids, such as 50, 100, 150, 200 or the entire length of the parent protein, polypeptide or peptide, optionally wherein the alignment is the best fit with gaps permitted.

[0045] Identity can be determined by comparing each position in aligned sequences. A degree of identity between amino acid sequences is a function of the number of identical or matching amino acids at positions shared by the sequences, i.e. over a specified region. Optimal pairwise alignment of sequences for comparisons of identity may be conducted using a variety of algorithms, as are known in the art, including the Clustal Omega program available at http://www.ebi.ac.uk/Tools/msa/clustalo/, the local homology algorithm of Smith and Waterman, 1981, Adv. Appl. Math 2: 482, the homology alignment algorithm of Needleman and Wunsch, 1970, J. Mol. Biol. 48:443, the search for similarity method of Pearson and Lipman, 1988, Proc. Natl. Acad. Sci. USA 85: 2444, and the computerized implementations of these algorithms (such as GAP, BESTFIT, FASTA and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, Madison, Wis., U.S.A.). Sequence identity may also be determined using the BLAST algorithm, described in Altschul et al., 1990, J. Mol. Biol. 215:403-10 (using the published default settings). Software for performing BLAST analysis may be available through the National Center for Biotechnology Information (through the internet at http://www.ncbi.nlm.nih.gov/). Such algorithms that calculate percent sequence identity generally account for sequence gaps and mismatches over the comparison region or area. For example, a BLAST (e.g., BLAST 2.0) search algorithm (see, e.g., Altschul et al., J. Mol. Biol. 215:403 (1990), publicly available through NCBI) has exemplary search parameters as follows: Mismatch -2; gap open 5; gap extension 2. For polypeptide sequence comparisons, a BLASTP algorithm is typically used in combination with a scoring matrix, such as PAM100, PAM 250, BLOSUM 62 or BLOSUM 50. FASTA (e.g., FASTA2 and FASTA3) and SSEARCH sequence comparison programs are also used to quantitate the extent of identity (Pearson et al., Proc. Natl. Acad. Sci. USA 85:2444 (1988); Pearson, Methods Mol. Biol. 132:185 (2000); and Smith et al., J. Mol. Biol. 147:195 (1981)). Programs for quantitating protein structural similarity using Delaunay-based topological mapping have also been developed (Bostick et al., Biochem Biophys Res Commun. 304:320 (2003)). Thus, a polypeptide having an amino acid sequence with at least, for example, 85 percent identity to the sequence with SEQ ID NO: 1, it is intended that the amino acid sequence of the polypeptide, after global pairwise alignment with the sequence SEQ ID NO: 1, may include up to 15 amino acid modifications per each 100 amino acids of the sequence SEQ ID NO: 1. That is to say that to obtain a polypeptide having an amino acid sequence at least 85 percent identical to the sequence SEQ ID NO: 1, up to 15 percent (15 of 100) of the amino acid residues in the subject sequence may be inserted, deleted, or substituted with another amino acid.

[0046] As used herein, the term "immune response" includes T cell (cellular) mediated and/or B cell (humoral) mediated immune responses, or both cellular and humoral responses. In particular, the term "immune response" may include an IgE-mediated immune response (i.e. an allergic immune response). Exemplary immune responses include T cell responses, such as Th2 responses resulting in cytokine production and/or cellular cytotoxicity. In addition, the term "immune response" includes responses that are indirectly affected by T cell activation, e.g., antibody production (humoral responses) and activation of cytokine responsive cells, e.g., eosinophils, macrophages. Immune cells involved in the immune response include lymphocytes, such as T cells (CD4+, CD8+, Th1 and Th2 cells, memory T cells, regulatory T cells) and B cells; antigen presenting cells (e.g., professional antigen presenting cells such as dendritic cells, macrophages, B lymphocytes, Langerhans cells, and non-professional antigen presenting cells such as keratinocytes, endothelial cells, astrocytes, fibroblasts, oligodendrocytes); natural killer (NK) cells; and myeloid cells, such as macrophages, eosinophils, mast cells, basophils, and granulocytes. A particular immune response is production of immunoglobulin (Ig) isotype antibodies or decreasing IgE antibodies.

Specific Embodiments of the Invention

Embodiments of the First Aspect of the Invention

[0047] The polypeptide comprising or consisting of

[0048] (a) an amino acid sequence selected from the group consisting of any one of SEQ ID NOs: 1-44 and 261-332, or

[0049] (b) an amino acid sequence consisting of at least or exactly 9 contiguous amino acid residues from the amino acid sequence of (a), or

[0050] (c) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of (a), or

[0051] (d) an amino acid sequence having a sequence identity of at least 60% with the amino acid sequence of (b)

[0052] constitutes the first aspect of the invention. In other words, apart from the polypeptides defined by SEQ ID NOs: 1-44 and 261-332, the invention also provides fragments and amino acid sequence variants of these proteins which can be useful in eliciting an immune response such as for example a specific T-cell response and IgG production.

[0053] Thus, a first aspect of the invention includes the option that a polypeptide of option (a) comprises an amino acid sequence variant of any one of SEQ ID NOs: 1-44 and 261-332. Hence, the sequence identity specified in option (c) is in some embodiments at least 65%, such as at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and at least 99%. The variant sequence may have the same biological activity or functionality as the parent polypeptide of option (a). For example, a variant sequence may have the same enzymatic functionality. The variant sequence may optionally have the same, greater or less ability to elicit, stimulate or induce an immune response (e.g. in vitro T cell proliferation or T cell cytokine production, such as the cytokines, IL-4, IL-5, IL-13 and/or IL-10); to induce immunological tolerance against the original polypeptide and/or to bind or interact with IgE, IgG or IgA antibodies raised against the parent polypeptide.

[0054] As mentioned, a first aspect of the invention includes the option (b) that polypeptides are fragments of the polypeptides of option (a) as well as the option (d) which comprises an amino acid sequence variant of polypeptides of option (b) that may still be useful in eliciting an immune response such as for example a specific T-cell response and IgG production.

[0055] Hence, the sequence identity specified in option (d) is in some embodiments at least 60%, such as at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, and at least 99%. The variant sequence defined in option (d) may have the same biological activity or functionality as the parent sequence defined in option (b). For example, a variant sequence may have the same enzymatic functionality (i.e. ability to act on the same substrate(s)). The variant sequence may optionally have the same, greater or less ability to

[0056] elicit, stimulate or induce an immune response (e.g. effecting in vitro T cell proliferation or T cell cytokine production (for example of the cytokines, IL-4, IL-5, IL-13 and/or IL-10)) in blood from mite allergic individuals;

[0057] to induce immunological tolerance against mites, a mite allergen or the parent polypeptide of option (b); and/or

[0058] to bind or interact with IgE, IgG or IgA antibodies raised against the parent polypeptide.

[0059] For polypeptides of more limited length, for example in the range of 9-30 amino acids in length, the variant sequence may result in the same, greater or less ability to bind a Class HLA II allele or a group of Class HLA II alleles. For example, a variant sequence may bind to at least 70%, such as at least 75%, 80%, 85%, 90% or 95% of the Class HLA II alleles that the parent polypeptide of option (b) binds to. The ability of the parent polypeptide and the variant sequence to bind HLA Class II alleles may be tested under the same test conditions, for example by use of HLA binding prediction tool or in-vitro HLA binding assay. For example, the binding of polypeptide of the invention may be investigated to one or more of the following Class HLA II alleles: DPA1*02:01-DPB1*01:01, DPA1*01:03-DPB1*02:01, DPA1*01:03-DPB1*03:01, DPA1*01:03-DPB1*04:01, DPA1*01:03-DPB1*04:02, DPA1*02:02-DPB1*05:01, DPA1*02:01-DPB1*14:01, DQA1*05:01-DQB1*02:01, DQA1*05:01-DQB1*03:01, DQA1*03:01-DQB1*03:02, DQA1*04:01-DQB1*04:02, DQA1*01:01-DQB1*05:01, DQA1*01:02-DQB1*06:02, DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:05, DRB1*07:01, DRB1*09:01, DRB1*11:01, DRB1*12:01, DRB1*13:02, DRB1*15:01, DRB3*01:01, DRB3*02:02, DRB4*01:01 and DRB5*01:01.

[0060] A polypeptide of option (b) and (d) may be of any length. In some embodiments, the polypeptides may be useful for peptide immunotherapy and comprise a limited number of amino acid residues. For example, a polypeptide of option (b) and (d) may consist of 9 to 30 amino acid residues, such as having a length of 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acid residues. As mentioned, such polypeptides of option (b) or (d) may comprise at least or exactly 9 contiguous amino acid residues, such as at least or exactly or at most 10, at least or exactly or at most 11, at least or exactly or at most 12, at least or exactly or at most 13, at least or exactly or at most 14, at least or exactly or at most 15, at least or exactly or at most 16, at least or exactly or at most 17, at least or exactly or at most 18, at least or exactly or at most 19, at least or exactly or at most 20, at least or exactly or at most 21, at least or exactly or at most 22, at least or exactly or at most 23, at least or exactly or at most 24, at least or exactly or at most 25, at least or exactly or at most 26, at least or exactly or at most 27 at least or exactly or at most 28, at least or exactly or at most 29, at least or exactly or at most 30 contiguous amino acid residues. In such embodiments, the consecutive amino acids of option (b) and (d) may comprise a T cell epitope, optionally a Th.sub.2 cell epitope.

[0061] In other embodiments, a polypeptide of option (b) or (d) may comprise several amino acid residues. Hence, in option (b) or (d), the at least or exactly 9 contiguous amino acid residues may constitute at least or exactly or at most 31, at least or exactly or at most 32, at least or exactly or at most 33, at least or exactly or at most 34, at least or exactly or at most 35, at least or exactly or at most 36, at least or exactly or at most 37, at least or exactly or at most 38, at least or exactly or at most 39, at least or exactly or at most 40, at least or exactly or at most 41, at least or exactly or at most 42, at least or exactly or at most 43, at least or exactly or at most 44, at least or exactly or at most 45, at least or exactly or at most 46, at least or exactly or at most 47, at least or exactly or at most 48, at least or exactly or at most 49, at least or exactly or at most 50, at least or exactly or at most 51, at least or exactly or at most 52, at least or exactly or at most 53, at least or exactly or at most 54, at least or exactly or at most 55, at least or exactly or at most 56, at least or exactly or at most 57, at least or exactly or at most 58, at least or exactly or at most 59, at least or exactly or at most 60, at least or exactly or at most 61, at least or exactly or at most 62, at least or exactly or at most 63, at least or exactly or at most 64, at least or exactly or at most 65, at least or exactly or at most 66, at least or exactly or at most 67, at least or exactly or at most 68, at least or exactly or at most 69, at least or exactly or at most 70, at least or exactly or at most 71, at least or exactly or at most 72, at least or exactly or at most 73, at least or exactly or at most 74, at least or exactly or at most 75, at least or exactly or at most 76, at least or exactly or at most 77, at least or exactly or at most 78, at least or exactly or at most 79, at least or exactly or at most 80, at least or exactly or at most 81, at least or exactly or at most 82, at least or exactly or at most 83, at least or exactly or at most 84, at least or exactly or at most 85, at least or exactly or at most 86, at least or exactly or at most 87, at least or exactly or at most 88, at least or exactly or at most 89, at least or exactly or at most 90, at least or exactly or at most 91, at least or exactly or at most 92, at least or exactly or at most 93, at least or exactly or at most 94, at least or exactly or at most 95, at least or exactly or at most 96, at least or exactly or at most 97, at least or exactly or at most 98, at least or exactly or at most 99, at least or exactly or at most 100, at least or exactly or at most 101, at least or exactly or at most 102, at least or exactly or at most 103, at least or exactly or at most 104, at least or exactly or at most 105, at least or exactly or at most 106, at least or exactly or at most 107, at least or exactly or at most 108, at least or exactly or at most 109, at least or exactly or at most 110, at least or exactly or at most 111, at least or exactly or at most 112, at least or exactly or at most 113, at least or exactly or at most 114, at least or exactly or at most 115, at least or exactly or at most 116, at least or exactly or at most 117, at least or exactly or at most 118, at least or exactly or at most 119, at least or exactly or at most 120, at least or exactly or at most 121, at least or exactly or at most 122, at least or exactly or at most 123, at least or exactly or at most 124, or at least or exactly or at most 125 contiguous amino acid residues.

[0062] The number of contiguous amino acids in option (b) and (d) can be higher for all of SEQ ID NOs: 1-44 and 261-304, 306-318, and 320-332. Another way to phrase this is that for each of SEQ ID NOs: 2-44 and 262-304, the number of the contiguous amino acid residues is at least or exactly or at most N-n, where N is the length of the sequence ID in question and n is any integer between 1 and N-9; that is, the at least 9 contiguous amino acids can be at least any number between 9 and the length of the reference sequence minus one, in increments of one. Consequently:

[0063] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 1-44, 261-304, 306-318, and 320-332, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 126, at least or exactly or at most 127, at least or exactly or at most 128, or at least or exactly or at most 129 contiguous amino acid residues.

[0064] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 2-44 262-304, 306-318, and 320-332, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 130 or at least or exactly or at most 131 contiguous amino acid residues.

[0065] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 4-44, 264-304, 306-318, and 320-332, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 132 or at least or exactly or at most 133 contiguous amino acid residues.

[0066] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 5-44, 265-304, 306-318, and 320-332, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 134, at least or exactly or at most 135, or at least or exactly or at most 136 contiguous amino acid residues.

[0067] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 5-44, 265-304, 306-314. 316-318, 320-328, and 330-332, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 137, at least or exactly or at most 138, at least or exactly or at most 139, at least or exactly or at most 140, at least or exactly or at most 141, at least or exactly or at most 142, at least or exactly or at most 143, at least or exactly or at most 144, at least or exactly or at most 145, at least or exactly or at most 146, at least or exactly or at most 147, at least or exactly or at most 148, or at least or exactly or at most 149 contiguous amino acid residues.

[0068] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 5-44 265-304, 306-313, 316-318, 320-327, and 330-332, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute, at least or exactly or at most 150, at least or exactly or at most 151 contiguous amino acid residues.

[0069] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 7-44, 267-304, 306-313, 316-318, 320-327, and 330-332, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 152 or at least or exactly or at most 153 contiguous amino acid residues.

[0070] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 9-44, 269-304, 306-313, 316-318, 320-327, and 330-332 the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 154, at least or exactly or at most 155, at least or exactly or at most 156, at least or exactly or at most 157, at least or exactly or at most 158, at least or exactly or at most 159, at least or exactly or at most 160, at least or exactly or at most 161, at least or exactly or at most 162, at least or exactly or at most 163, at least or exactly or at most 164, at least or exactly or at most 165, at least or exactly or at most 166, at least or exactly or at most 167, at least or exactly or at most 168, at least or exactly or at most 169, or at least or exactly or at most 170 contiguous amino acid residues.

[0071] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 10-44, 270-304, 306-313, 316-318, 320-327, and 330-332, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 171 contiguous amino acid residues.

[0072] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 11-44, 271-304, 306-313, 316-318, 320-327, and 330-332, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 172, at least or exactly or at most 173, at least or exactly or at most 174, at least or exactly or at most 175, at least or exactly or at most 176, at least or exactly or at most 177, at least or exactly or at most 178, at least or exactly or at most 179, at least or exactly or at most 180, at least or exactly or at most 181, at least or exactly or at most 182, at least or exactly or at most 183, at least or exactly or at most 184, or at least or exactly or at most 185 contiguous amino acid residues Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 11-44, 271-304, 306-313, 316-317, 320-327, and 330-331, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 186, or at least or exactly or at most 187 contiguous amino acid residues.

[0073] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 13-44, 273-304, 306-313, 316-317, 320-327, and 330-331, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 188, at least or exactly or at most 189, at least or exactly or at most 190, at least or exactly or at most 191, at least or exactly or at most 192, at least or exactly or at most 193, at least or exactly or at most 194, at least or exactly or at most 195, at least or exactly or at most 196, at least or exactly or at most 197, at least or exactly or at most 198, at least or exactly or at most 199, at least or exactly or at most 200, at least or exactly or at most 201, at least or exactly or at most 202, at least or exactly or at most 203, at least or exactly or at most 204, at least or exactly or at most 205, at least or exactly or at most 206, at least or exactly or at most 207, at least or exactly or at most 208, at least or exactly or at most 209, at least or exactly or at most 210, at least or exactly or at most 211, at least or exactly or at most 212, at least or exactly or at most 213, at least or exactly or at most 214, at least or exactly or at most 215, at least or exactly or at most 216, at least or exactly or at most 217, at least or exactly or at most 218, at least or exactly or at most 219, at least or exactly or at most 220, or at least or exactly or at most 221 contiguous amino acid residues.

[0074] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 15-44, 275-304, 306-313, 316-317, 320-327, and 330-331, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 222, at least or exactly or at most 223, at least or exactly or at most 224, at least or exactly or at most 225, at least or exactly or at most 226, or at least or exactly or at most 227 contiguous amino acid residues.

[0075] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 17-44, 277-304, 306-313, 316-317, 320-327, and 330-331, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 228 contiguous amino acid residues.

[0076] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 17, 19-44, 277, 279-304, 306-313, 316-317, 320-327, and 330-331, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 229, at least or exactly or at most 230, or at least or exactly or at most 231 contiguous amino acid residues.

[0077] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 17, 19-44, 277, 279-304, 306-313, 317, 320-327, and 331, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 232 contiguous amino acid residues.

[0078] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 19-44, 279-304, 306-313, 317, 320-327, and 331, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 233, at least or exactly or at most 234, at least or exactly or at most 235, at least or exactly or at most 236, at least or exactly or at most 237, at least or exactly or at most 238, at least or exactly or at most 239, at least or exactly or at most 240, at least or exactly or at most 241, at least or exactly or at most 242, at least or exactly or at most 243, at least or exactly or at most 244, at least or exactly or at most 245, at least or exactly or at most 246, at least or exactly or at most 247, at least or exactly or at most 248, at least or exactly or at most 249, at least or exactly or at most 250, or at least or exactly or at most 251 contiguous amino acid residues.

[0079] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 20-44, 280-304, 306-313, and 320-327, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 252 contiguous amino acid residues.

[0080] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 21-44 and 281-304, 306-313, and 320-327, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 253, at least or exactly or at most 254, at least or exactly or at most 255, at least or exactly or at most 256, at least or exactly or at most 257, at least or exactly or at most 258, or at least or exactly or at most 259 contiguous amino acid residues.

[0081] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 21-44 and 281-304, 306-312, and 320-326, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 260 contiguous amino acid residues.

[0082] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 22-44, 282-304, 306-312, and 320-326, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 261 contiguous amino acid residues.

[0083] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 23-44, 283-304, 306-312, and 320-326, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 262, at least or exactly or at most 263, at least or exactly or at most 264, at least or exactly or at most 265, at least or exactly or at most 266, at least or exactly or at most 267, at least or exactly or at most 268, or at least or exactly or at most 269 contiguous amino acid residues.

[0084] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 24-44, 284-304, 306-312, and 320-326, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 270 contiguous amino acid residues.

[0085] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 25-44, 285-304, 306-312, and 320-326, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 271, at least or exactly or at most 272, at least or exactly or at most 273, or at least or exactly or at most 274 contiguous amino acid residues.

[0086] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 26-44, 286-304, 306-312, and 320-326, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 275, at least or exactly or at most 276, at least or exactly or at most 277, at least or exactly or at most 278, at least or exactly or at most 279, at least or exactly or at most 280, at least or exactly or at most 281, at least or exactly or at most 282, at least or exactly or at most 283, at least or exactly or at most 284, at least or exactly or at most 285, at least or exactly or at most 286, at least or exactly or at most 287, at least or exactly or at most 288, at least or exactly or at most 289, at least or exactly or at most 290, at least or exactly or at most 291, at least or exactly or at most 292, at least or exactly or at most 293, at least or exactly or at most 294, at least or exactly or at most 295, at least or exactly or at most 296, at least or exactly or at most 297, at least or exactly or at most 298, at least or exactly or at most 299, at least or exactly or at most 300, at least or exactly or at most 301, at least or exactly or at most 302, at least or exactly or at most 303, at least or exactly or at most 304, at least or exactly or at most 305, at least or exactly or at most 306, at least or exactly or at most 307, or at least or exactly or at most 308 contiguous amino acid residues.

[0087] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 26-44, 286-304, 306-311, and 320-325, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 309 contiguous amino acid residues.

[0088] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 27-44, 287-304, 306-311, and 320-325, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 310, at least or exactly or at most 311, at least or exactly or at most 312, at least or exactly or at most 313, at least or exactly or at most 314, at least or exactly or at most 315, at least or exactly or at most 316, at least or exactly or at most 317, at least or exactly or at most 318, at least or exactly or at most 319, or at least or exactly or at most 320 contiguous amino acid residues.

[0089] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 28-44, 288-304, 306-311, and 320-325, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 321, at least or exactly or at most 322, at least or exactly or at most 323, at least or exactly or at most 324, at least or exactly or at most 325, at least or exactly or at most 326, at least or exactly or at most 327, at least or exactly or at most 328, at least or exactly or at most 329, at least or exactly or at most 330, or at least or exactly or at most 331 contiguous amino acid residues.

[0090] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 30-44, 290-304, 306-311, and 320-325, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 332, at least or exactly or at most 333, at least or exactly or at most 334, at least or exactly or at most 335, at least or exactly or at most 336, at least or exactly or at most 337, at least or exactly or at most 338, at least or exactly or at most 339, at least or exactly or at most 340, at least or exactly or at most 341, at least or exactly or at most 342, at least or exactly or at most 343, at least or exactly or at most 344, at least or exactly or at most 345, at least or exactly or at most 346, at least or exactly or at most 347, at least or exactly or at most 348, at least or exactly or at most 349, at least or exactly or at most 350, at least or exactly or at most 351, at least or exactly or at most 352, at least or exactly or at most 353, at least or exactly or at most 354, at least or exactly or at most 355, at least or exactly or at most 356, at least or exactly or at most 357, at least or exactly or at most 358, at least or exactly or at most 359, or at least or exactly or at most 360 contiguous amino acid residues.

[0091] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 31-44, 291-304, 306-311, and 320-325, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 361 contiguous amino acid residues.

[0092] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 32-44 and 292-304, 306-311, and 320-325, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 362 contiguous amino acid residues.

[0093] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 32-44 and 292-304, 307-311, and 321-325, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 363, at least or exactly or at most 364, at least or exactly or at most 365, at least or exactly or at most 366, at least or exactly or at most 367, at least or exactly or at most 368, at least or exactly or at most 369, at least or exactly or at most 370, at least or exactly or at most 371, at least or exactly or at most 372, at least or exactly or at most 373, at least or exactly or at most 374, at least or exactly or at most 375, at least or exactly or at most 376, at least or exactly or at most 377, at least or exactly or at most 378, at least or exactly or at most 379, at least or exactly or at most 380, at least or exactly or at most 381, at least or exactly or at most 382, at least or exactly or at most 383, at least or exactly or at most 384, at least or exactly or at most 385, at least or exactly or at most 386, at least or exactly or at most 387, at least or exactly or at most 388, at least or exactly or at most 389, at least or exactly or at most 390, at least or exactly or at most 391, at least or exactly or at most 392, at least or exactly or at most 393, at least or exactly or at most 394, at least or exactly or at most 395, at least or exactly or at most 396, at least or exactly or at most 397, at least or exactly or at most 398, at least or exactly or at most 399, at least or exactly or at most 400, at least or exactly or at most 401, at least or exactly or at most 402, at least or exactly or at most 403, at least or exactly or at most 404, at least or exactly or at most 405, at least or exactly or at most 406, at least or exactly or at most 407, at least or exactly or at most 408, at least or exactly or at most 409, at least or exactly or at most 410, at least or exactly or at most 411, at least or exactly or at most 412, at least or exactly or at most 413, at least or exactly or at most 414, at least or exactly or at most 415, at least or exactly or at most 416, at least or exactly or at most 417, at least or exactly or at most 418, at least or exactly or at most 419, at least or exactly or at most 420, at least or exactly or at most 421, at least or exactly or at most 422, at least or exactly or at most 423, at least or exactly or at most 424, at least or exactly or at most 425, at least or exactly or at most 426, at least or exactly or at most 427, or at least or exactly or at most 428 contiguous amino acid residues.

[0094] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 33-44, 293-304, 307-311, and 321-325, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 429, at least or exactly or at most 430, at least or exactly or at most 431, at least or exactly or at most 432, at least or exactly or at most 433 contiguous amino acid residues.

[0095] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 34-44, 294-304, 307-311, and 321-325, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 434, at least or exactly or at most 435, at least or exactly or at most 436, at least or exactly or at most 437, at least or exactly or at most 438, at least or exactly or at most 439, at least or exactly or at most 440, at least or exactly or at most 441, at least or exactly or at most 442, at least or exactly or at most 443, at least or exactly or at most 444, at least or exactly or at most 445, at least or exactly or at most 446, at least or exactly or at most 447, at least or exactly or at most 448, at least or exactly or at most 449, at least or exactly or at most 450, at least or exactly or at most 451, at least or exactly or at most 452, at least or exactly or at most 453, at least or exactly or at most 454, at least or exactly or at most 455, at least or exactly or at most 456, at least or exactly or at most 457, or at least or exactly or at most 458 contiguous amino acid residues.

[0096] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 34-44, 294-304, 307-310, and 321-324, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 459, at least or exactly or at most 460, or at least or exactly or at most 461 contiguous amino acid residues.

[0097] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 36-44, 296-304, 307-310, and 321-324, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 462 contiguous amino acid residues.

[0098] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 37-44, 297-304, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 463, at least or exactly or at most 464, at least or exactly or at most 465, at least or exactly or at most 466, at least or exactly or at most 467, at least or exactly or at most 468, at least or exactly or at most 469, at least or exactly or at most 470, at least or exactly or at most 471, at least or exactly or at most 472, or at least or exactly or at most 473 contiguous amino acid residues.

[0099] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 38-44, 298-304, 307-310, and 321-324, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 474, at least or exactly or at most 475, at least or exactly or at most 476, at least or exactly or at most 477, at least or exactly or at most 478, at least or exactly or at most 479, at least or exactly or at most 480, or at least or exactly or at most 481 contiguous amino acid residues.

[0100] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 38-44, 298-304, 307, 308, 310, 321, 322, and 324, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 482, at least or exactly or at most 483, at least or exactly or at most 484, at least or exactly or at most 485, at least or exactly or at most 486, at least or exactly or at most 487, at least or exactly or at most 488, at least or exactly or at most 489, or at least or exactly or at most 490 contiguous amino acid residues.

[0101] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 38-44, 298-304, 307, 308, 321, and 322, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 491, at least or exactly or at most 492, at least or exactly or at most 493, at least or exactly or at most 494, at least or exactly or at most 495, at least or exactly or at most 496, at least or exactly or at most 497, at least or exactly or at most 498, at least or exactly or at most 499, at least or exactly or at most 500, at least or exactly or at most 501, at least or exactly or at most 502, at least or exactly or at most 503, at least or exactly or at most 504, at least or exactly or at most 505, at least or exactly or at most 506, at least or exactly or at most 507, or at least or exactly or at most 508 contiguous amino acid residues.

[0102] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 39-44, 299-304, 307, 308, 321, and 321, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 509, at least or exactly or at most 510, at least or exactly or at most 511, at least or exactly or at most 512, at least or exactly or at most 513, at least or exactly or at most 514, at least or exactly or at most 515, at least or exactly or at most 516, at least or exactly or at most 517, at least or exactly or at most 518 contiguous amino acid residues.

[0103] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 39, 41-44, 299, 301-304, 307, 308, 321, and 321, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 519 contiguous amino acid residues.

[0104] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 41-44, 301-304, 307, 308, 321, and 322, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 520, at least or exactly or at most 521, at least or exactly or at most 522, at least or exactly or at most 523, at least or exactly or at most 524, at least or exactly or at most 525, at least or exactly or at most 526, at least or exactly or at most 527, at least or exactly or at most 528, at least or exactly or at most 529, at least or exactly or at most 530, at least or exactly or at most 531, at least or exactly or at most 532, at least or exactly or at most 533, at least or exactly or at most 534, at least or exactly or at most 535, at least or exactly or at most 536, at least or exactly or at most 537, at least or exactly or at most 538, at least or exactly or at most 539, at least or exactly or at most 540, at least or exactly or at most 541, at least or exactly or at most 542, at least or exactly or at most 543, at least or exactly or at most 544, at least or exactly or at most 545, at least or exactly or at most 546, at least or exactly or at most 547, at least or exactly or at most 548, at least or exactly or at most 549, at least or exactly or at most 550, at least or exactly or at most 551, at least or exactly or at most 552, at least or exactly or at most 553, at least or exactly or at most 554, at least or exactly or at most 555, at least or exactly or at most 556, at least or exactly or at most 557, at least or exactly or at most 558, at least or exactly or at most 559, at least or exactly or at most 560, at least or exactly or at most 561, at least or exactly or at most 562, at least or exactly or at most 563, at least or exactly or at most 564, at least or exactly or at most 565, at least or exactly or at most 566, at least or exactly or at most 567, at least or exactly or at most 568, at least or exactly or at most 569, at least or exactly or at most 570, at least or exactly or at most 571, at least or exactly or at most 572, at least or exactly or at most 573, at least or exactly or at most 574, at least or exactly or at most 575, at least or exactly or at most 576, at least or exactly or at most 577, at least or exactly or at most 578, at least or exactly or at most 579, at least or exactly or at most 580, at least or exactly or at most 581, at least or exactly or at most 582, at least or exactly or at most 583, at least or exactly or at most 584, at least or exactly or at most 585, at least or exactly or at most 586, at least or exactly or at most 587, at least or exactly or at most 588, at least or exactly or at most 589, at least or exactly or at most 590, at least or exactly or at most 591, at least or exactly or at most 592, at least or exactly or at most 593, at least or exactly or at most 594, at least or exactly or at most 595, at least or exactly or at most 596, at least or exactly or at most 597, at least or exactly or at most 598, at least or exactly or at most 599, at least or exactly or at most 600, at least or exactly or at most 601, at least or exactly or at most 602, at least or exactly or at most 603, at least or exactly or at most 604, at least or exactly or at most 605, at least or exactly or at most 606, at least or exactly or at most 607, at least or exactly or at most 608, at least or exactly or at most 609, at least or exactly or at most 610, at least or exactly or at most 611, at least or exactly or at most 612, at least or exactly or at most 613, at least or exactly or at most 614, at least or exactly or at most 615, at least or exactly or at most 616, at least or exactly or at most 617, at least or exactly or at most 618, at least or exactly or at most 619, at least or exactly or at most 620, at least or exactly or at most 621, at least or exactly or at most 622, at least or exactly or at most 623, at least or exactly or at most 624, at least or exactly or at most 625, at least or exactly or at most 626, at least or exactly or at most 627, at least or exactly or at most 628, at least or exactly or at most 629, at least or exactly or at most 630, at least or exactly or at most 631, at least or exactly or at most 632, at least or exactly or at most 633, at least or exactly or at most 634, at least or exactly or at most 635, at least or exactly or at most 636, at least or exactly or at most 637, at least or exactly or at most 638, at least or exactly or at most 639, at least or exactly or at most 640, at least or exactly or at most 641, at least or exactly or at most 642, at least or exactly or at most 643, at least or exactly or at most 644, at least or exactly or at most 645, at least or exactly or at most 646, at least or exactly or at most 647, at least or exactly or at most 648, at least or exactly or at most 649, at least or exactly or at most 650, at least or exactly or at most 651, at least or exactly or at most 652, at least or exactly or at most 653, at least or exactly or at most 654, at least or exactly or at most 655, at least or exactly or at most 656, at least or exactly or at most 657, at least or exactly or at most 658, at least or exactly or at most 659, at least or exactly or at most 660, at least or exactly or at most 661, at least or exactly or at most 662, at least or exactly or at most 663, at least or exactly or at most 664, at least or exactly or at most 665, at least or exactly or at most 666, at least or exactly or at most 667, at least or exactly or at most 668, at least or exactly or at most 669, at least or exactly or at most 670, at least or exactly or at most 671, at least or exactly or at most 672, at least or exactly or at most 673, at least or exactly or at most 674, at least or exactly or at most 675, at least or exactly or at most 676, at least or exactly or at most 677, at least or exactly or at most 678, at least or exactly or at most 679, at least or exactly or at most 680, at least or exactly or at most 681, at least or exactly or at most 682, at least or exactly or at most 683, at least or exactly or at most 684, at least or exactly or at most 685, at least or exactly or at most 686, at least or exactly or at most 687, at least or exactly or at most 688, at least or exactly or at most 689, at least or exactly or at most 690, at least or exactly or at most 691, at least or exactly or at most 692, at least or exactly or at most 693, at least or exactly or at most 694, at least or exactly or at most 695, at least or exactly or at most 696, at least or exactly or at most 697, at least or exactly or at most 698, at least or exactly or at most 699, at least or exactly or at most 700, at least or exactly or at most 701, at least or exactly or at most 702, at least or exactly or at most 703, at least or exactly or at most 704, at least or exactly or at most 705, at least or exactly or at most 706, at least or exactly or at most 707, at least or exactly or at most 708, at least or exactly or at most 709, at least or exactly or at most 710, at least or exactly or at most 711, at least or exactly or at most 712, at least or exactly or at most 713, at least or exactly or at most 714, at least or exactly or at most 715, at least or exactly or at most 716, at least or exactly or at most 717, at least or exactly or at most 718, at least or exactly or at most 719, at least or exactly or at most 720, at least or exactly or at most 721, at least or exactly or at most 722, at least or exactly or at most 723, at least or exactly or at most 724, at least or exactly or at most 725, at least or exactly or at most 726, at least or exactly or at most 727, at least or exactly or at most 728, at least or exactly or at most 729, at least or exactly or at most 730, at least or exactly or at most 731, at least or exactly or at most 732, at least or exactly or at most 733, at least or exactly or at most 734, at least or exactly or at most 735, at least or exactly or at most 736, at least or exactly or at most 737, at least or exactly or at most 738, at least or exactly or at most 739, at least or exactly or at most 740, at least or exactly or at most 741, at least or exactly or at most 742, at least or exactly or at most 743, at least or exactly or at most 744, at least or exactly or at most 745, at least or exactly or at most 746, at least or exactly or at most 747, at least or exactly or at most 748, at least or exactly or at most 749, at least or exactly or at most 750, at least or exactly or at most 751, at least or exactly or at most 752, at least or exactly or at most 753, at least or exactly or at most 754, at least or exactly or at most 755, at least or exactly or at most 756, at least or exactly or at most 757, at least or exactly or at most 758, at least or exactly or at most 759, at least or exactly or at most 760, at least or exactly or at most 761, at least or exactly or at most 762, at least or exactly or at most 763, at least or exactly or at most 764, at least or exactly or at most 765, at least or exactly or at most 766, at least or exactly or at most 767, at least or exactly or at most 768, at least or exactly or at most 769, at least or exactly or at most 770, at least or exactly or at most 771, at least or exactly or at most 772, at least or exactly or at most 773, at least or exactly or at most 774, at least or exactly or at most 775, at least or exactly or at most 776, at least or exactly or at most 777, at least or exactly or at most 778, at least or exactly or at most 779, at least or exactly or at most 780, at least or exactly or at most 781, at least or exactly or at most 782, at least or exactly or at most 783, at least or exactly or at most 784, at least or exactly or at most 785, at least or exactly or at most 786, at least or exactly or at most 787, at least or exactly or at most 788, at least or exactly or at most 789, at least or exactly or at most 790, at least or exactly or at most 791, at least or exactly or at most 792, at least or exactly or at most 793, at least or exactly or at most 794, at least or exactly or at most 795, at least or exactly or at most 796, at least or exactly or at most 797, at least or exactly or at most 798, at least or exactly or at most 799, at least or exactly or at most 800, at least or exactly or at most 801, at least or exactly or at most 802, at least or exactly or at most 803, at least or exactly or at most 804, at least or exactly or at most 805, at least or exactly or at most 806, at least or exactly or at most 807, at least or exactly or at most 808, at least or exactly or at most 809, at least or exactly or at most 810, at least or exactly or at most 811, at least or exactly or at most 812, at least or exactly or at most 813, at least or exactly or at most 814, at least or exactly or at most 815, at least or exactly or at most 816, at least or exactly or at most 817, at least or exactly or at most 818, at least or exactly or at most 819, at least or exactly or at most 820, at least or exactly or at most 821, at least or exactly or at most 822, at least or exactly or at most 823, at least or exactly or at most 824, at least or exactly or at most 825, at least or exactly or at most 826, at least or exactly or at most 827, at least or exactly or at most 828, at least or exactly or at most 829, at least or exactly or at most 830, at least or exactly or at most 831, at least or exactly or at most 832, at least or exactly or at most 833, at least or exactly or at most 834, at least or exactly or at most 835, at least or exactly or at most 836, at least or exactly or at most 837, at least or exactly or at most 838, at least or exactly or at most 839, at least or exactly or at most 840, at least or exactly or at most 841, at least or exactly or at most 842, at least or exactly or at most 843, at least or exactly or at most 844, at least or exactly or at most 845, at least or exactly or at most 846, at least or exactly or at most 847, at least or exactly or at most 848, at least or exactly or at most 849, at least or exactly or at most 850, at least or exactly or at most 851, at least or exactly or at most 852, at least or exactly or at most 853, at least or exactly or at most 854, at least or exactly or at most 855, at least or exactly or at most 856, at least or exactly or at most 857, at least or exactly or at most 858, at least or exactly or at most 859, at least or exactly or at most 860, at least or exactly or at most 861, at least or exactly or at most 862, at least or exactly or at most 863, at least or exactly or at most 864, at least or exactly or at most 865, at least or exactly or at most 866, at least or exactly or at most 867, at least or exactly or at most 868, at least or exactly or at most 869, at least or exactly or at most 870, at least or exactly or at most 871, at least or exactly or at most 872, at least or exactly or at most 873, at least or exactly or at most 874, at least or exactly or at most 875, at least or exactly or at most 876, at least or exactly or at most 877, at least or exactly or at most 878, at least or exactly or at most 879, at least or exactly or at most 880, at least or exactly or at most 881, at least or exactly or at most 882, at least or exactly or at most 883, or at least or exactly or at most 884 contiguous amino acid residues.

[0105] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 41, 43, 44, 302, 303, and 304, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 885 or at least or exactly or at most 886 contiguous amino acid residues.

[0106] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 43-44, 303-304, 307, 308, 321, and 322, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 887 or at least or exactly or at most 888 contiguous amino acid residues.

[0107] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 43-44, 303-304, 307, and 321, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 889, at least or exactly or at most 890, at least or exactly or at most 891, at least or exactly or at most 892, at least or exactly or at most 893, at least or exactly or at most 894, at least or exactly or at most 895, at least or exactly or at most 896, at least or exactly or at most 897, at least or exactly or at most 898, at least or exactly or at most 899, at least or exactly or at most 900, at least or exactly or at most 901, at least or exactly or at most 902, at least or exactly or at most 903, at least or exactly or at most 904, at least or exactly or at most 905, at least or exactly or at most 906, at least or exactly or at most 907, at least or exactly or at most 908, at least or exactly or at most 909, at least or exactly or at most 910, at least or exactly or at most 911, at least or exactly or at most 912, at least or exactly or at most 913, at least or exactly or at most 914, at least or exactly or at most 915, at least or exactly or at most 916, at least or exactly or at most 917, at least or exactly or at most 918, at least or exactly or at most 919, at least or exactly or at most 920, at least or exactly or at most 921, at least or exactly or at most 922, at least or exactly or at most 923, at least or exactly or at most 924, at least or exactly or at most 925, at least or exactly or at most 926, at least or exactly or at most 927, at least or exactly or at most 928, at least or exactly or at most 929, at least or exactly or at most 930, at least or exactly or at most 931, at least or exactly or at most 932, at least or exactly or at most 933, at least or exactly or at most 934, at least or exactly or at most 935, at least or exactly or at most 936, at least or exactly or at most 937, at least or exactly or at most 938, at least or exactly or at most 939, at least or exactly or at most 940, at least or exactly or at most 941, at least or exactly or at most 942, at least or exactly or at most 943, at least or exactly or at most 944, at least or exactly or at most 945, at least or exactly or at most 946, at least or exactly or at most 947, at least or exactly or at most 948, at least or exactly or at most 949, at least or exactly or at most 950, at least or exactly or at most 951, at least or exactly or at most 952, at least or exactly or at most 953, at least or exactly or at most 954, at least or exactly or at most 955, at least or exactly or at most 956, at least or exactly or at most 957, at least or exactly or at most 958, at least or exactly or at most 959, at least or exactly or at most 960, at least or exactly or at most 961, at least or exactly or at most 962, at least or exactly or at most 963, at least or exactly or at most 964, at least or exactly or at most 965, at least or exactly or at most 966, at least or exactly or at most 967, at least or exactly or at most 968, at least or exactly or at most 969, at least or exactly or at most 970, at least or exactly or at most 971, or at least or exactly or at most 972 contiguous amino acid residues.

[0108] Insofar as embodiment (b) and (d) relate to SEQ ID NOs: 43-44, and 303-304, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 973, or at least or exactly or at most 974 contiguous amino acid residues.

[0109] Finally, insofar as embodiment (b) and (d) relate to SEQ ID NOs: 44 and 304, the at least 9 contiguous amino acids referred to in option (b) in the definition of the first aspect of the invention may also constitute at least or exactly or at most 975, at least or exactly or at most 976, at least or exactly or at most 977, at least or exactly or at most 978, at least or exactly or at most 979, at least or exactly or at most 980, at least or exactly or at most 981, at least or exactly or at most 982, at least or exactly or at most 983, at least or exactly or at most 984, at least or exactly or at most 985, at least or exactly or at most 986, at least or exactly or at most 987, at least or exactly or at most 988, or at least or exactly or at most 989 contiguous amino acid residues.

[0110] In any one of the embodiments of option (b) and (d) above, the polypeptide of the invention is also one that has at least or exactly 9 contiguous amino acid residues defined for option (b) above in any one of the embodiments and wherein the contiguous amino acid residues commence

[0111] at amino acid residue 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, or 117 in any one of SEQ ID NOs: 1-44 and 261-332; or

[0112] at amino acid residue 118, 119, 120, 121, or 122 in any one of SEQ ID NOs: 1-44, 261-304, 306-318, and 320-332; or

[0113] at amino acid residue 123 or 124 in any one of SEQ ID NOs: 2-44, 262-304, 306-318, and 320-332; or

[0114] at amino acid residue 125 or 126 in any one of SEQ ID NOs: 4-44, 264-304, 306-318, and 320-332; or

[0115] at amino acid residue 127, 128, or 129 in any one of SEQ ID NOs: 5-44, 265-304, 306-318, and 320-332; or

[0116] at amino acid residue 130, 131, 132, 133, 134, 135, 136, 135, 136, 137, 138, 139, 140, 141, 142 in any one of SEQ ID NOs: 5-44, 265-304, 306-314, 316-318, 320-328, and 330-332; or

[0117] at amino acid residue, 143 or 144 in any one of SEQ ID NOs: 5-44, 265-304, 306-313, 316-318, 320-327, and 330-332; or

[0118] at amino acid residue 145 and 146 in any one of SEQ ID NOs: 7-44, 267-304, 306-313, 316-318, 320-327, and 330-332; or

[0119] at amino acid residue 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, or 163 in any one of SEQ ID NOs: 9-44, 269-304, 306-313, 316-318, 320-327, and 330-332; or

[0120] at amino acid residue 164 in any one of SEQ ID NOs: 10-44, 270-304, 306-313, 316-318, 320-327, and 330-332; or

[0121] at amino acid residue 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178 in any one of SEQ ID NOs: 11-44, 271-304, 306-313, 316-318, 320-327, and 330-332; or

[0122] at amino acid residue 179 or 180 in any one of SEQ ID NOs: 11-44 and 271-304, 306-313, 316-317, 320-327, and 330-331; or

[0123] at amino acid residue 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, or 214 in any one of SEQ ID NOs: 13-44, 273-304, 306-313, 316-317, 320-327, and 330-331; or

[0124] at amino acid residue 215, 216, 217, 218, 219, or 220 in any one of SEQ ID NOs: in any one of SEQ ID NOs: 15-44, 275-304, 306-313, 316-317, 320-327, and 330-331; or

[0125] at amino acid residue 221 in any one of SEQ ID NOs: 17-44 and 275-304; or

[0126] at amino acid residue 222, 223, or 224 in any one of SEQ ID NOs: 17, 19-44, 277, 279-304, 306-313, 316-317, 320-327, and 330-331; or

[0127] at amino acid residue 225 in any one of SEQ ID NOs: 17, 19-44, 277, 279-304, 306-313, 317, 320-327, and 331; or

[0128] at amino acid residue 226, 227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240, 241, 242, 243, or 244 in any one of SEQ ID NOs: 19-44, 279-304, 306-313, 317, 320-327, and 331; or

[0129] at amino acid residue 245 in any one of SEQ ID NOs: 20-44, 280-304, 306-313, and 320-327; or

[0130] at amino acid residue 246, 247, 248, 249, 250, 251, or 252 in any one of SEQ ID NOs: 21-44 and 281-304, 306-313, and 320-327; or at amino acid residue 253 in any one of SEQ ID NOs: 21-44, 281-304, 306-312, and 320-326; or

[0131] at amino acid residue 254 in any one of SEQ ID NOs: 22-44 and 282-304; or

[0132] at amino acid residue 255, 256, 257, 258, 259, 260, 261, or 262 in any one of SEQ ID NOs: 23-44, 283-304, 306-312, and 320-326; or at amino acid residue 263 in any one of SEQ ID NOs: in any one of SEQ ID NOs: 24-44, 284-304, 306-312, and 320-326; or

[0133] at amino acid residue 264, 265, 266, or 267 in any one of SEQ ID NOs: 25-44, 285-304, 306-312, and 320-326; or

[0134] at amino acid residue 268, 269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282, 283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296, 297, 298, 299, 300, 301 in any one of SEQ ID NOs: 26-44, 286-304, 306-312, and 320-326; or

[0135] at amino acid residue 302 in any one of SEQ ID NOs: 26-44, 286-304, 306-311, and 320-325; or

[0136] at amino acid residue, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312, or 313 in any one of SEQ ID NOs: 27-44, 287-304, 306-311, and 320-325; or

[0137] at amino acid residue 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, or 324 in any one of SEQ ID NOs: 28-44, 288-304, 306-311, and 320-325; or

[0138] at amino acid residue 325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, or 353 in any one of SEQ ID NOs: 30-44, 290-304, 306-311, and 320-325; or

[0139] at amino acid residue 354 in any one of SEQ ID NOs: 31-44 291-304, 306-311, and 320-325; or

[0140] at amino acid residue 355 in any one of SEQ ID NOs: 32-44 292-304, 306-311, and 320-325; or

[0141] at amino acid residue 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366, 367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, or 421 in any one of SEQ ID NOs: 32-44, 292-304, 307-311, and 321-325; or

[0142] at amino acid residue 422, 423, 424, 425, or 426 in any one of SEQ ID NOs: 33-44, 293-304, 307-311, and 321-325; or at amino acid residue 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450, 451 in any one of SEQ ID NOs: 34-44, 294-304, 307-311, and 321-325; or

[0143] at amino acid residue 452, 453, or 454 in any one of SEQ ID NOs: 34-44, 294-304, 307-310, and 321-324; or at amino acid residue 455 in any one of SEQ ID NOs: 36-44, 296-304, 307-310, and 321-324; or

[0144] at amino acid residue 456, 457, 458, 459, 460, 461, 462, 463, 464, 465, or 466 in any one of SEQ ID NOs: 37-44, 297-304, 307-310, and 321-324; or

[0145] at amino acid residue 467, 468, 469, 470, 471, 472, 473, or 474 in any one of SEQ ID NOs: 38-44, 298-304, 307-310, and 321-324; or

[0146] at amino acid residue 475, 476, 477, 478, 479, 480, 481, 482, or 483 in any one of SEQ ID NOs: 38-44, 298-304, 307, 308, 310, 321, 323, and 324; or

[0147] at amino acid residue 484, 485, 486, 487, 488, 489, 490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, or 501 in any one of SEQ ID NOs: 38-44, 298-304, 307, 308, 321, and 323; or

[0148] at amino acid residue 502, 503, 504, 505, 506, 507, 508, 509, 510, or 511 in any one of SEQ ID NOs: 39-44, 299-304, 307, 308, 321, and 323; or

[0149] at amino acid residue 512 in any one of SEQ ID NOs: 39, 41-44, 299, 301-304, 307, 308, 321, and 323; or

[0150] at amino acid residue 513, 514, 515, 516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702, 703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842, 843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855, 856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868, 869, 870, 871, 872, 873, 874, 875, 876, or 877 in any one of SEQ ID NOs: 41-44 301-304, 307, 308, 321, and 323; or

[0151] at amino acid residue 878 or 879 in any one of SEQ ID NOs: 41, 43, 44, 301, 303, 304, 307, 308, 321, and 323; or

[0152] at amino acid residue 880 or 881 in any one of SEQ ID NOs: 43, 44, 303, 304, 307, 308, 321, and 323; or

[0153] at amino acid residue, 882, 883, 884, 885, 886, 887, 888, 889, 890, 891, 892, 893, 894, 895, 896, 897, 898, 899, 900, 901, 902, 903, 904, 905, 906, 907, 908, 909, 910, 911, 912, 913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924, 925, 926, 927, 928, 929, 930, 931, 932, 933, 934, 935, 936, 937, 938, 939, 940, 941, 942, 943, 944, 945, 946, 947, 948, 949, 950, 951, 952, 953, 954, 955, 956, 957, 958, 959, 960, 961, 962, 963, 964, 965 in any one of SEQ ID NOs: 43, 44, 303, 304, 307, and 321; or

[0154] at amino acid residue, 966 or 967 in any one of SEQ ID NOs: 43, 44, 303, and 304; or

[0155] at amino acid residue 968, 969, 970, 971, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, or 982 in SEQ ID NO: 44 or 304.

[0156] The possible commencement point in the sequences listed above is of course dependent on the number of contiguous amino acid residues (L) selected: the N-terminal first residue cannot in any case be higher numbered than N-L+1, where N is the number of amino acid residues of the sequence among SEQ ID NOs: 1-44 and 261-332 in which the contiguous amino acid residues are found.

[0157] As will be apparent from the examples, certain peptides are particularly interesting embodiments of the first aspect of the invention: These embodiments of the first aspect relate to a polypeptide, optionally of 9 to 30 amino acid residues in length, comprise or consist of an amino acid sequence consisting of

[0158] 9, 10, 11, 12, 13, 14 or 15 consecutive amino acid residues from a parent sequence selected from any one of SEQ ID NOs: 45-260 and any one of SEQ ID NOs: 45, 61, 63, 80, 100, 113, 147, 154, 170, 172, 191, 215, 225, 226, 248, and 260, wherein any cysteine residue is/are substituted with a serine residue, an alanine residue or a 2-aminobutyric acid residue, or

[0159] a variant of 9 consecutive amino acid residues from a parent sequence selected from any one of SEQ ID NOs: 45-260, wherein 1 or 2 or 3 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent sequence, or

[0160] a variant of 10 consecutive amino acid residues from a parent sequence selected from any one of SEQ ID NOs: 45-260, wherein 1 or 2 or 3 or 4 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent sequence, or

[0161] a variant of 11 consecutive amino acid residues from a parent sequence selected from any one of SEQ ID NOs: 45-260, wherein 1 or 2 or 3 or 4 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent sequence, or

[0162] a variant of 12 consecutive amino acid residues from a parent sequence selected from any one of SEQ ID NOs: 45-260, wherein 1 or 2 or 3 or 4 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent sequence, or

[0163] a variant of 13 consecutive amino acid residues from a parent sequence selected from any one of SEQ ID NOs: 45-260, wherein 1, 2, 3, 4, or 5 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent sequence, or

[0164] a variant of 14 consecutive amino acid residues from a parent sequence selected from any one of SEQ ID NOs: 45-260, wherein 1, 2, 3, 4, or 5 amino acid residues are substituted with a different amino acid residue in the variant relative to the parent sequence, or

[0165] a variant of a parent sequence selected from any one of SEQ ID NOs: 45-260, wherein 1, 2, 3, 4, 5, or 6 amino acids are substituted with a different amino acid in the variant relative to the parent sequence.

[0166] In these embodiments, the parent sequence may commence at

[0167] residue 1, 2, 3, 4, 5, 6, or 7 in any one of SEQ ID NOs: 45-260 when the peptide is 9 amino acids in length, or

[0168] residue 1, 2, 3, 4, 5, or 6 in any one of SEQ ID NOs: 45-260 when the peptide is 10 amino acids in length, or

[0169] residue 1, 2, 3, 3, 4, or 5 in any one of SEQ ID NOs: 45-260 when the peptide is 11 amino acids in length, or

[0170] residue 1, 2, 3, or 4 in any one of SEQ ID NOs: 45-260 when the peptide is 12 amino acids in length, or

[0171] residue 1, 2, or 3 in any one of SEQ ID NOs: 45-260 when the peptide is 13 amino acids in length, or

[0172] residue 1 or 2 in any one of SEQ ID NOs: 45-260 when the peptide is 14 amino acids in length.

[0173] Thus, in some embodiments of the polypeptide of the first aspect of the invention, the polypeptide comprises or consists of 9 to 15 consecutive amino acid residues of an amino acid sequence set forth in any one of SEQ ID NOs: 45-260 or a variant sequence thereof wherein 1, 2, 3, 4, 5, or 6 amino acids are substituted with a different amino acid in the variant relative to the parent sequence. In such embodiments, the polypeptide may have a length of 9-30 amino acid residues or more, for example 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30, or optionally more amino acid residues.

[0174] The variant sequence may have the same biological activity or functionality as the parent sequence as defined of polypeptides of option (b) of the first aspect. For example, the variant sequence may result in the same, greater or less ability to bind a Class HLA II allele or a group of Class HLA II alleles or the variant sequence may comprise a T cell epitope, optionally a Th2 cell epitope. Optionally, the Class HLA II binding is determined with respect to a particular group of Class HLA II alleles, for example one or more or all of the following alleles: DPA1*02:01-DPB1*01:01, DPA1*01:03-DPB1*02:01, DPA1*01:03-DPB1*03:01, DPA1*01:03-DPB1*04:01, DPA1*01:03-DPB1*04:02, DPA1*02:02-DPB1*05:01, DPA1*02:01-DPB1*14:01, DQA1*05:01-DQB1*02:01, DQA1*05:01-DQB1*03:01, DQA1*03:01-DQB1*03:02, DQA1*04:01-DQB1*04:02, DQA1*01:01-DQB1*05:01, DQA1*01:02-DQB1*06:02, DRB1*01:01, DRB1*03:01, DRB1*04:01, DRB1*04:05, DRB1*07:01, DRB1*09:01, DRB1*11:01, DRB1*12:01, DRB1*13:02, DRB1*15:01, DRB3*01:01, DRB3*02:02, DRB4*01:01 and DRB5*01:01.

[0175] The polypeptide of the first aspect of the invention may in certain embodiments find special use in qualitative or quantitative mass spectrometric determination of polypeptides. In these embodiments, the polypeptide of the invention typically consists of an amino acid sequence identical with the amino acid sequence of a proteolytic fragment of a protein consisting of an amino acid sequence selected from any one of SEQ ID NOs: 1-44, and 261-332 (preferably SEQ ID NOs 1-44 and 305-318, i.e. proteolytic fragments of naturally occurring proteins). Such a proteolytic fragment is typically a tryptic or chymotryptic fragment, but any suitable protease can be used to provide the proteolytic fragment: papain, pepsin, ArgC, LysC, V8 protease, AspN, pronase, and carboxypeptidease C. In certain embodiments, the polypeptide, which has the amino acid sequence of a proteolytic fragment will also include a mass modifying label; see infra for a discussion of labels useful in qMS.

Embodiments of the Second Aspect of the Invention

[0176] A composition of the second aspect of the invention comprises one or more of the polypeptides of the first aspect of the invention. When the composition is for pharmaceutical use, it further comprises a pharmaceutically acceptable carrier, excipient and/or adjuvant, optionally sterile. It will typically be formulated as a vaccine for parenteral or sublingual administration.

[0177] Any suitable administration form is useful for the pharmaceutical composition, but one particularly relevant form is a powder, optionally formulated to be re-dissolved before use.

[0178] Also, fast-dispersing tablets (optionally freeze dried) suitable for sublingual administration or buccal administration are of relevance.

[0179] The pharmaceutical composition may be a vaccine, e.g. a product for use in conducting immunotherapy, including but not limited to a vaccine for treating an allergic immune response to mites. The vaccine may be formulated for parenteral administration, such as by subcutaneous, intradermal, transcutaneous administration, e.g. formulated as a powder that optionally may be re-dissolved before use.

[0180] A pharmaceutical composition comprises in addition to the peptide combination, therapeutically inactive ingredients, such as pharmaceutically acceptable or physiologically acceptable excipient(s), carrier(s) and/or adjuvant(s), which are well-known to the person skilled in the art and may include, but are not limited to, solvents, emulsifiers, wetting agents, plasticizers, solubilizers (e.g. solubility enhancing agents), coloring substances, fillers, preservatives, anti-oxidants, anti-microbial agents, viscosity adjusting agents, buffering agents, pH adjusting agents, isotonicity adjusting agents, mucoadhesive substances, and the like. Examples of formulation strategies are well-known to the person skilled in the art.

[0181] In some embodiments, the peptide(s) may be formulated (e.g. mixed together) with immune-modifying agents like adjuvants usually applied in immunotherapy products.

[0182] In some embodiments, the pharmaceutical composition may be formulated for parenteral administration, such as formulated for injection, e.g. subcutaneous and/or intradermal injection. Therefore, in some embodiments, the pharmaceutical composition may be a liquid (i.e. formulated as a liquid), including a solution, a suspension, a dispersion, and a gelled liquid. A liquid pharmaceutical composition may be formed by dissolving a powder, granulate or lyophilizate of a peptide combination described herein in a suitable solvent and then administering to a subject. Suitable solvents may be any solvent having physiologically acceptable properties and able to dissolve the peptide combination in desired concentrations. A desired concentration may depend on the aliquot to be administered (i.e. to be injected) and the desired single dose. It is emphasized that for the purpose of injection the aliquot is in the range of about 10 to 500 microliters, e.g. 50 to 300 microliters or less and a desired single dose is within range of 1 to 1000 nanomoles. Typically the concentration of each peptide is the same, such as in an equimolar concentration, but each peptide of the composition may also be present in different concentrations. Typically, the solvent is an aqueous solution, optionally mixed with other solvents. Thus, a solvent may comprise at least 60% w/w of water, e.g. at least 65% w/w, 70% w/w, 75% w/w, 80% w/w, 85% w/w, 90% w/w or 95% w/w, 99% w/w of water, such as distilled water, such as sterile water. In some embodiments, the solvent is sterile distilled water, e.g. water for injection. An aqueous solution may comprise other solvents than water, for example DMSO (dimethylsulfoxide), glycerol, ethanol, acetonitrile, vegetable or synthetic oils. The pH of the aqueous phase of the solvent may be in a physiological acceptable range, typically in the range of 3 to 9, such as in the range of pH 3 to 8, such as in the range of pH 4 to 8, such as in the range of pH 5 to 8, such as in the range of pH 6 to 8. Thus, the liquid formulation may comprise a pH controlling agent or buffering agent (e.g. citrate buffer, phosphate buffer, acetate buffer), optionally the pH may be adjusted with dilutions of strong base (e.g. sodium hydroxide or the like) and/or dilutions of strong acids (e.g. hydrochloric acid).

[0183] Typically, the liquid formulation is isotonic, and optionally sterile. Therefore, in some embodiments, the formulation comprises saline, such as isotonic saline. The liquid may contain additional excipients, such as another solvent, a solubilizing enhancing agent, ionic and non-ionic emulsifiers, a dispersant, a thickener, a preservative, an anti-microbial agent, and/or an antioxidant. Non-limiting illustrative examples of solvents include water, saline, DMSO, glycerol, ethanol, acetonitrile, vegetable or synthetic oils.

[0184] Typically, the freeze-dried composition may be dissolved before use, for example dissolved in an aqueous, optionally sterile, solution, for example a solution having a pH in the range of 3-9, such as a pH in the range of 3-8, such as a pH in the range of 4-8. A lyophilizate may contain additional ingredients, e.g. bulking agents and lyoprotectants, buffering, antioxidants, antimicrobial agents, solubilizers.

[0185] A freeze-dried composition may also be formulated into a solid dosage form that is administered for example by the oral route such as by oral mucosa. Thus, in some embodiments, the pharmaceutical composition may be formulated for oral administration, for example for sublingual administration. Therefore, the pharmaceutical composition may be a solid dosage form, such as a freeze-dried solid dosage form, typically a tablet, a capsule or sachet, which optionally may be formulated for fast disintegration. Pharmaceutical formulations and delivery systems appropriate for the compositions, methods and uses of the invention are known in the art (see, e.g., Remington: The Science and Practice of Pharmacy (2003) 20th ed., Mack Publishing Co., Easton, Pa.; Remington's Pharmaceutical Sciences (1990) 18th ed., Mack Publishing Co., Easton, Pa.; The Merck Index (1996) 12th ed., Merck Publishing Group, Whitehouse, N.J.; Pharmaceutical Principles of Solid Dosage Forms (1993), Technonic Publishing Co., Inc., Lancaster, Pa.; Ansel ad Soklosa, Pharmaceutical Calculations (2001) 11th ed., Lippincott Williams & Wilkins, Baltimore, Md.; and Poznansky et al., Drug Delivery Systems (1980), R. L. Juliano, ed., Oxford, N.Y., pp. 253-315).

[0186] Peptides may be prone to degradation when exposed to oxygen, for example when exposed to air or solvents containing air. Therefore, in some embodiments, the pharmaceutical composition comprises an inert gas, e.g. argon or nitrogen.

Embodiments Relating to the Third Aspect of the Invention

[0187] As set forth above, the third aspect relates to a method of treating allergy in a patient, where signs or symptoms of said allergy are elicited in the patient by exposure to house dust mites or storage mites and/or exposure to at least one protein allergen present in house dust mites or storage mites, the method comprising administering, to the patient, a therapeutically effective amount of a polypeptide of the first aspect of the invention, optionally two or more polypeptides of the first aspect of the invention or a composition of the second aspect of the invention.

[0188] As discussed above, the inventors have found that the polypeptides of SEQ ID NOs: 1-44 appear to be generally non-allergenic in many patients, thus rendering them highly safe as immunogens used in anti-allergy therapy. It cannot be excluded that occasional patients will be allergic (e.g. have raised IgE antibodies against one or more of the sequences of SEQ ID NOs: 1-44), but it is generally understood that it is advantageous that patients subjected to the immunogens according to the invention are non-allergic towards the protein from which the immunogen is derived, meaning that it is attempted to avoid to treat those patients having detectable IgE levels against the polypeptides of SEQ ID NOs: 1-44 with said polypeptides or a T cell-epitope-containing fragment thereof. Hence, in embodiments of the first aspect, the polypeptide used for the administration is one, wherein exposure of the patient to the polypeptide does not elicit signs or symptoms of allergy in the patient. Regarding signs or symptoms of allergy, cf. below for further discussion, but it is generally understood that this means signs or symptoms of IgE mediated allergy including that the patient has elicited IgE-antibodies against the polypeptide.

[0189] While true prophylaxis of allergy is not excluded when carrying out the method of the third aspect of the invention, it is expected that the method will find particular use in patients that have already experienced mite allergy or have raised IgE antibodies against a mite allergen. Therefore, all embodiments of the third aspect may entail or consist of treating the allergy by relieving or reducing an immune response triggered by exposure to the mites or the protein allergen. Also, treating the allergy can in all embodiments of the third aspect comprise or consist of relieving one or more signs/symptoms of an immune response triggered by exposure to the mites or the protein allergen. Moreover, treating the allergy may in all embodiments of the third aspect consist of or comprise induction of immunological tolerance against the mites or the protein allergen. And treating the allergy may in all embodiments of the third aspect comprise or consist of relieving one or more signs/symptom(s) associated with allergic rhinitis and/or allergic conjunctivitis and/or allergic asthma and/or allergic eczema (e.g. atopic dermatitis).

[0190] The signs/symptoms of allergy mentioned above are those typically associated with the allergies treated according to the present invention, typically signs/symptoms may include one or more of the following; itchy running nose, itchy watery eyes, itchy skin and shortness of breath and the patient may experience that the signs/symptoms will to some extent be relieved by treatment with antihistamines or steroids. In a clinical setting, the signs and symptoms may include detectable levels of IgE antibodies against one or more the mites of interest.

[0191] In the event that the treatment entails or consists of relieving one or more signs or symptoms associated with allergic rhinitis, the relief is typically

[0192] reduction of the intensity of itchy nose and/or

[0193] reduction of the number of sneezes within a given period (e.g. daily, weekly, monthly) and/or

[0194] reduction of the intensity of blocked nose (congestion) and/or

[0195] reduction of the amount of nasal fluid and/or

[0196] reduction of the eosinophilic count in nasal fluid and/or

[0197] reduction of specific IgE antibody level (titre) in nasal fluid or in serum and/or

[0198] reduction of basophil histamine release in blood.

[0199] It is to be noted that a "sign" of allergy is an objectively observable characteristic of the disease, whereas a "symptom" is the patient's subjective experience(s) relative to the disease. Some signs can be symptoms and vice versa, but if a patient for instance experiences dizziness due to a disease, this can only be categorized as a symptom, because it is not objectively observable by anybody else than the patient. On the other hand, increasing levels of for example IgE-antibodies is a "sign", since it cannot be sensed by the patient but it can be objectively measured in an appropriate assay.

[0200] Where treating the allergy comprises or consists of relieving one or more signs or symptoms associated with allergic conjunctivitis, the relief typically comprises

[0201] reducing the intensity of itchy eyes, redness in the white of the eyes and/or watery eyes; and/or

[0202] reducing the eosinophilic count in conjunctival tissue scrapings; and/or

[0203] reducing specific IgE antibody level (titer) in conjunctival tissue scrapings or in serum; and/or

[0204] reducing basophil histamine release in blood.

[0205] Where treating the allergy comprises or consists of relieving one or more signs or symptoms associated with allergic asthma, the relief typically comprises

[0206] reducing the intensity and/or number of coughs within a given period (e.g. daily, weekly, monthly); and/or

[0207] reducing the intensity of wheezes; and/or

[0208] improving being short of breath; and/or

[0209] improving lung function; and/or

[0210] reducing specific IgE antibody level (titre) in lung fluid or in serum; and/or

[0211] reducing basophil histamine release in blood.

[0212] Where treating the allergy comprises or consists of relieving one or more signs or symptoms associated with atopic dermatitis, the relief typically comprises

[0213] reducing itch intensity of the skin; and/or

[0214] reducing eczema score; and/or

[0215] reducing number of (peripheral) blood eosinophils.

[0216] In all embodiments of the third aspect of the invention, the method may comprise or consist of reducing the patient's need for concomitant treatment with corticosteroids or H1 antihistamines to reduce, relieve, or suppress one or more symptoms of an immune response associated with the allergy. In other words, these embodiments have the long term benefit of reducing the patient's need for medication.

[0217] As used herein, the term "immunological tolerance" refers to a) a decreased or reduced level of a specific immunological response (thought to be mediated at least in part by antigen-specific effector T lymphocytes, B lymphocytes, antibodies, or a combination thereof); b) a delay in the onset or progression of a specific immunological response; or c) a reduced risk of the onset or progression of a specific immunological response to mites. An increase, improvement, enhancement or induction of "tolerance" may refer to a decrease, reduction, inhibition, suppression, or limiting or controlling or clearing of specific immunological reactivity to an allergen as compared to reactivity to the allergen in a previous exposure to the same allergen. Thus, in certain embodiments, the method comprises inducing immunological tolerance in a subject to mites, e.g. to an allergen of mites discussed herein to suppress an allergic immune response to the allergen. Immunological tolerance in a subject to an allergen can also be reflected by reducing the occurrence, frequency, severity, progression, or duration of an allergic response of the subject to the allergen. Induction of immune tolerance (also referred to as desensitization), and the relative amount of immune tolerance, can be measured by methods disclosed herein or known to the skilled artisan. For example, induction of immune tolerance can be measured by the modulated lymphokine and/or cytokine level in a subject or animal before versus after administering a peptide combination described herein for the first time. A modulated cytokine level can be an increase of a cytokine level, for instance an increase of a lymphokine and/or cytokine level of at least 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 20, 50 times or more relative to before administering the peptide combination for the first time. Alternatively, modulation can be a decrease of the level of a particular cytokine level, for instance a decrease of the lymphokine and/or cytokine level of at least 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 20, 50 times or more relative to before administering a peptide combination for the first time. The lymphokines/cytokines chosen to be measured can be from any relevant lymphokines/cytokines, such as IL-2, IL-5, IL-4, IL-6, IL-10, IL-12, IL-13, IL-17, TNF-alfa, IFN-gamma, TGF-beta, MCP-1, RANK-L and FIt3L. Accordingly, the term "inducing immunological tolerance" may include eliciting, stimulating, promoting, increasing or enhancing immunological tolerance. Immunological tolerance may involve modulation of T cell activity, including but not limited to CD4+ T cells, CD8+ T cells, Th1 cells, Th2 cells and regulatory T cells (Tregs), and memory T cells, including inflammatory lymphokines/cytokines produced by T cells.

[0218] The patients subjected to the treatment of the third aspect of the invention typically present with an immune response clinically presented as atopic dermatitis, urticaria, contact dermatitis, allergic conjunctivitis, allergic rhinitis, allergic asthma, anapylaxis, and/or hay fever. In particular advantageous versions of any one of the embodiments of the third aspect of the invention, the treatment thus decreases, reduces, suppresses or inhibits atopic dermatitis, urticaria, contact dermatitis, allergic conjunctivitis, allergic rhinitis, allergic asthma, anaphylaxis, and/or hay fever.

[0219] Without being bound to any theory, it is believed that the method of the third aspect of the invention is capable of increasing an IgG antibody response in the patient to a protein allergen of the mites and/or of decreasing an IgE antibody response in the patient to a protein allergen of the mites and/or of decreasing a T cell response in the patient against a protein allergen of the mites, since each one of these physiological effects have a beneficial effect on the signs and symptoms of allergy. Hence, in advantageous versions of all embodiments of the third aspect of the invention, the method does provide for increasing an IgG antibody response in the patient to a protein allergen of the mites and/or for decreasing an IgE antibody response in the patient to a protein allergen of the mites and/or for decreasing a T cell response in the patient against a protein allergen of the mites.

[0220] It will be understood that the patients that are subjected to the method of the third aspect of the invention are typically sensitized to at least one protein allergen of the mites. It is to be understood that such patients may exhibit allergy signs or experience symptoms of allergy, but it is not excluded that "patients" that merely exhibit clinical signs of being sensitized against at least one protein allergy of the mites will also benefit from the treatment.

[0221] The allergy treated according to the invention is in all embodiments of the third aspect of the invention allergy towards house dust mites of the genus Dermatophagoides (for example selected from the group consisting of Dermatophagoides pteronyssinus, Dermatophagoides farinae) or of the genus Euroglyphus (for example Euroglyphus maynei), or wherein the mites are storage mites of the genus Glycyphagus, Lepidoglyphus, Tyrophagus, or Blomia (for example Glycyphagus domesticus, Lepidoglyphus destructor, Tyrophagus putrescentiae, or Blomia tropicalis).

[0222] Consequently, the protein allergen is in all embodiments of the third aspect of the invention selected from one or more protein allergens in the groups consisting of

[0223] a group 1 allergen of mites (for example a group 1 allergen of a house dust mite (e.g. Der p 1, Der f 1, or Eur m 1, or a group 1 allergen of a storage mite, e.g. Gly d 1, Lep d 1, Typ p 1 and Blo t 1) and

[0224] a group 2 allergen of mites (for example a group 2 allergen of a house dust mite, e.g. Der p 2, Der f 2 and Eur m 2, and a group 2 allergen of a storage mite, e.g. Gly d 2, Lep d 2, Typ p 2 and Blo t 2).

[0225] As mentioned above, a particular embodiment of the third aspect of the invention entails that a polypeptide of the first aspect or a composition of the second aspect does not elicit signs or symptoms of allergy. These signs and symptoms are in important embodiments selected from the group consisting of:

[0226] the presence in the patient of specific IgE antibodies that binds to the a polypeptide of the first aspect or a composition of the second aspect (e.g. the level of specific IgE is below the detection level when tested in an assay measuring specific IgE (e.g. ImmunoCAP.RTM. Specific IgE Blood Test), for example the level is below 0.7 kU/L, when tested by an ImmunoCAP.RTM. test;

[0227] serum histamine release induced by a polypeptide of the first aspect or a composition of the second aspect is below the detection level when tested in a basophil activation test (BAT)

[0228] a positive skin prick test with a polypeptide of the first aspect or a composition of the second aspect; and

[0229] the signs or symptoms discussed in detail supra.

[0230] In certain embodiments of third aspect of the invention, a polypeptide of the first aspect or a composition of the second aspect is formulated together with a pharmaceutically and immunologically acceptable carrier, vehicle or excipient.

[0231] When exercising the method of the third aspect of the invention and any embodiment thereof, a polypeptide of the first aspect or a composition of the second aspect may further be formulated together with an immunological adjuvant. Also a polypeptide of the first aspect or a composition of the second aspect may be formulated with a suitable carrier, diluent, or vehicle.

[0232] It is particularly preferred that a polypeptide of the first aspect or a composition of the second aspect is administered by the parenteral route to the patient, such as via a route of administration selected from any one of subcutaneous, intradermal, epicutaneous, topical, sublingual, buccal, intranasal, respiratory and the intralymphatic route. In particular the sublingual and buccal routes are of interest.

[0233] A polypeptide of the first aspect or a composition of the second aspect may also be administered to a subject in need thereof by injection, such as by subcutaneous or intradermal administration, but may also include other routes of administration, such as epicutaneous, transcutaneous, topical, rectal, oral, intranasal, respiratory and intralymphatic route of administration.

[0234] Typically, the subject in need thereof is a human, a pet such as a dog or a cat, a domestic animal such as a horse, or a laboratory animal (a mouse, a guinea pig or a rabbit). The subject may be sensitized to mites (e.g. having specific IgE antibodies against an allergen of mites and/or having a T cell response against an allergen of mites). Therefore, a subject in need thereof may produce specific IgE antibodies or a T cell response against mite allergens.

[0235] A polypeptide of the first aspect or a composition of the second aspect may be formulated for injection or for sublingual administration (e.g. a solid dosage form such as a tablet, and in particular a freeze-dried tablet) or is formulated in a composition as described infra for the compositions of the invention.

[0236] Typically, a polypeptide of the first aspect or a composition of the second aspect is administered several times, i.e. repeatedly, such as in weekly, by-weekly, monthly or quarterly intervals.

[0237] As will be understood from the above, the allergy is, according to the third aspect of the invention and any embodiments thereof, preferably treated by immunotherapy. The patient in question need not be human, since many pets suffer from allergy towards the mites discussed above. As such, the patient may be human or a mammal, such as a cat, dog, and a horse.

[0238] A pharmacologically effective amount of a single dose of a polypeptide of the first aspect or a composition of the second aspect may be in the range of 1 to 1000 nanomole, for example 1 to 500 nanomole, for example 1 to 250 nanomole, for example 5 to 250 nanomole. Typically, a polypeptide or composition of the invention is administered as a liquid in a volume of about 50 to 150 microliter, such as by intradermal administration.

Embodiments of Diagnostic Aspects of the Invention

[0239] The fourth aspect of the invention relates to an in vitro method of determining whether T cells of a subject are responsive to one or more polypeptides of the first aspect or a composition of the second aspect. The method comprises contacting T cells obtained from the subject with said polypeptide(s) or composition(s) and determining whether the T cells are stimulated.

[0240] The fifth aspect of the invention relates to an in vitro method of diagnosing a subject for sensitization or allergy to house dust mites or storage mites, comprising contacting T cells obtained from the subject one or more polypeptides of the first aspect or a composition of the second aspect and determining whether the T cells are stimulated.

[0241] The sixth aspect of the invention relates to an in vitro method for determining whether a subject has, or is at risk of developing, an allergy to house dust mites or storage mites, comprising contacting T cells obtained from the subject with one or more polypeptides of the first aspect or a composition of the second aspect and determining whether the T cells are stimulated.

[0242] A number of assay formats are available for the purpose of determining T cell stimulation and are well known for the person skilled. For instance ELISPOT/Fluorospot, simple proliferation assays as well as the assay disclosed in Example 2 are all useful for the purpose of determining T cell responsiveness.

[0243] The seventh aspect of the invention relates to an in vitro method of diagnosing a subject for allergy or sensitivity to house dust mites or storage mites, comprising determining the presence of specific IgE against one or more polypeptides of the first aspect or a composition of the second aspect in a biological sample (e.g. serum, plasma or blood) obtained from the subject. Any conventional antibody based immune assay is useful for this purpose and include enzyme linked immune sorbent assays (ELISAs), radioimmune assays (RIAs), immunoblotting techniques, etc. but also cell based assays such as measurement of histamine release induced byan analyte in a basophil activation test (BAT).

[0244] The eighth aspect of the invention relates to a diagnostic kit comprising one or more polypeptides of the first aspect or a composition of the second aspect. Such a kit will normally also include necessary detection agents, visualisation means, carriers etc. that enable one or more of the above-described diagnostic assays.

Other Aspects of the Invention

[0245] The ninth aspect of the invention relates an isolated nucleic acid fragment, which comprises

[0246] i) a nucleotide sequence encoding a polypeptide according to the first aspect of the invention, or

[0247] ii) a nucleotide sequence complementary to the nucleotide sequence in i)-v).

[0248] A tenth aspect of the invention relates to a vector comprising a nucleic acid sequence of the invention, such as a cloning vector or an expression vector.

[0249] Such a vector conventionally may include, in operable linkage and in the 5'-3' direction,

[0250] an expression control region comprising an enhancer/promoter for driving expression of the nucleic acid fragment defined in option i) for the nucleic acid fragment of the invention,

[0251] an optional signal peptide coding sequence,

[0252] a nucleotide sequence defined in option i) for the nucleic acid of the invention, and

[0253] an optional terminator.

[0254] The expression control region may drive expression in prokaryotic cell such as a bacterium, e.g. in E. coli, but it may in certain instances be necessary to includes expression control regions suitable for eukaryotic cells and in certain cases this applies in particular to plant cells.

[0255] The vector may be capable of autonomous replication and/or it may be capable of being integrated into the genome of a host cell--the latter is of particular of relevance when constructing cells and cell lines that are capable of stable expression of the nucleic acid fragment of the invention.

[0256] Suitable vectors are a virus, such as an attenuated virus, a bacteriophage, a plasmid, a minichromosome, and a cosmid.

[0257] It will be understood that the nucleic acid fragments of the invention may be used for both production purposes, so such vectors will typically be in the form of cloning vectors or expression vectors.

[0258] Such a vector of the invention often comprises in operable linkage and in the 5'-3' direction, an expression control region comprising an enhancer/promoter for driving expression of the nucleic acid, an optional signal peptide coding sequence, a nucleotide sequence of the invention, and optionally a terminator. Hence, such a vector constitutes an expression vector useful for effecting production in cells of a polypeptide of the invention. Since the polypeptides of the invention are of mite origin, recombinant production has to be effected in host cells that can express the coding nucleic acid. Bacterial host cells may be used in some cases. However, if the vector is to drive expression in eukaryotic cell, the expression control region should be adapted to this particular use.

[0259] For production purposes it is therefore often convenient that the expression control region drives expression in a prokaryotic cell such as a bacterium, e.g. in E. coli, or in a eukaryotic cell such as a fungal cell, a plant cell, an insect cell, or a mammalian cell.

[0260] Also, for production purposes, it is practical that the vector is capable of integrating the nucleic acid into the genome of a selected host cell--this is particularly useful if the vector is use in the production of stably transformed cells, where the progeny will also include the genetic information introduced via the vector. Alternatively, vectors incapable of being integrated into the genome of a piscine host cell are useful in early screening of production cells.

[0261] Polypeptides of the invention may as indicated be encoded by a nucleic acid molecule comprised in a vector. A nucleic acid sequence can be "heterologous," which means that it is in a context foreign to the cell in which the vector is being introduced, which includes a sequence homologous to a sequence in the cell but in a position within the host cell where it is ordinarily not found.

[0262] Vectors include naked DNAs, RNAs, plasmids, cosmids, viruses (bacteriophage, animal viruses, and plant viruses), and artificial chromosomes (e.g., YACs). One of skill in the art would be well equipped to construct a vector through standard recombinant techniques. In addition to encoding the polypeptides of this invention, a vector of the present invention may encode polypeptide sequences such as a "tag" or immunogenicity enhancing peptide (e.g. an immunogenic carrier or a fusion partner that stimulates the immune system, such as a cytokine or active fragment thereof). Useful vectors encoding such fusion proteins include pIN vectors, vectors encoding a stretch of histidines, and pGEX vectors, for use in generating glutathione S-transferase (GST) soluble fusion proteins for later purification and separation or cleavage.

[0263] Vectors of the invention may be used in a host cell to produce a polypeptide of the invention that may subsequently be purified for administration.

[0264] Expression vectors can contain a variety of "control sequences," which refer to nucleic acid sequences necessary for the transcription and possibly translation of an operably linked coding sequence in a particular host cell. In addition to control sequences that govern transcription and translation, vectors and expression vectors may contain nucleic acid sequences that serve other functions as well and are described infra.

[0265] 1. Promoters and Enhancers

[0266] A "promoter" is a control sequence. The promoter is typically a region of a nucleic acid sequence at which initiation and rate of transcription are controlled. It may contain genetic elements at which regulatory proteins and molecules may bind such as RNA polymerase and other transcription factors. The phrases "operatively positioned," "operatively linked," "under control," and "under transcriptional control" mean that a promoter is in a correct functional location and/or orientation in relation to a nucleic acid sequence to control transcriptional initiation and expression of that sequence. A promoter may or may not be used in conjunction with an "enhancer," which refers to a cis-acting regulatory sequence involved in the transcriptional activation of a nucleic acid sequence.

[0267] A promoter may be one naturally associated with a gene or sequence, as may be obtained by isolating the 5' non-coding sequences located upstream of the coding segment or exon. Such a promoter can be referred to as "endogenous." Similarly, an enhancer may be one naturally associated with a nucleic acid sequence, located either downstream or upstream of that sequence. Alternatively, certain advantages will be gained by positioning the coding nucleic acid segment under the control of a recombinant or heterologous promoter, which refers to a promoter that is not normally associated with a nucleic acid sequence in its natural environment. A recombinant or heterologous enhancer refers also to an enhancer not normally associated with a nucleic acid sequence in its natural state. Such promoters or enhancers may include promoters or enhancers of other genes, and promoters or enhancers isolated from any other prokaryotic, viral, or eukaryotic cell, and promoters or enhancers not "naturally occurring," i.e., containing different elements of different transcriptional regulatory regions, and/or mutations that alter expression. In addition to producing nucleic acid sequences of promoters and enhancers synthetically, sequences may be produced using recombinant cloning and/or nucleic acid amplification technology, including polymerase chain reaction in connection with the compositions disclosed herein.

[0268] It may be important to employ a promoter and/or enhancer that effectively direct(s) the expression of the DNA segment in the cell type or organism chosen for expression. Those of skill in the art of molecular biology generally know the use of promoters, enhancers, and cell type combinations for protein expression. The promoters employed may be constitutive, tissue-specific, or inducible and in certain embodiments may direct high level expression of the introduced DNA segment under specified conditions, such as large-scale production of recombinant proteins or peptides.

[0269] Examples of inducible elements, which are regions of a nucleic acid sequence that can be activated in response to a specific stimulus, include but are not limited to Immunoglobulin Heavy Chain, Immunoglobulin Light Chain, T Cell Receptor, HLA DQa and/or DQI, 1-Interferon, Interleukin-2, Interleukin-2 Receptor, MHC Class II 5, MHC Class II HLA-DRa, 3-Actin, Muscle Creatine Kinase (MCK), Prealbumin (Transthyretin), Elastase I, Metallothionein (MTII), Collagenase, Albumin, .alpha.-Fetoprotein, .gamma.-Globin, .beta.-Globin, c-fos, c-HA-ras, Insulin, Neural Cell Adhesion Molecule (NCAM), al-Antitrypain, H2B (TH2B) Histone, Mouse and/or Type I Collagen, Glucose-Regulated Proteins (GRP94 and GRP78), Rat Growth Hormone, Human Serum Amyloid A (SAA), Troponin I (TN I), Platelet-Derived Growth Factor (PDGF), Duchenne Muscular Dystrophy, SV40, Polyoma, Retroviruses, Papilloma Virus, Hepatitis B Virus, Human Immunodeficiency Virus, Cytomegalovirus (CMV) IE, and Gibbon Ape Leukemia Virus.

[0270] Inducible Elements include MT II--Phorbol Ester (TFA)/Heavy metals; MMTV (mouse mammary tumor virus)--Glucocorticoids; .beta.-Interferon--poly(rl)x/poly(rc); Adenovirus 5 E2--EIA; Collagenase--Phorbol Ester (TPA); Stromelysin--Phorbol Ester (TPA); SV40--Phorbol Ester (TPA); Murine MX Gene--Interferon, Newcastle Disease Virus; GRP78 Gene--A23187; .alpha.-2-Macroglobulin--IL-6; Vimentin--Serum; MHC Class I Gene H-2.kappa.b--Interferon; HSP70--E1A/SV40 Large T Antigen; Proliferin--Phorbol Ester/TPA; Tumor Necrosis Factor--PMA; and Thyroid Stimulating Hormonea Gene--Thyroid Hormone.

[0271] Also contemplated as useful in the present invention are the dectin-1 and dectin-2 promoters. Additionally any promoter/enhancer combination (as per the Eukaryotic Promoter Data Base EPDB) could also be used to drive expression of structural genes encoding oligosaccharide processing enzymes, protein folding accessory proteins, selectable marker proteins or a heterologous protein of interest.

[0272] The particular promoter that is employed to control the expression of peptide or protein encoding polynucleotide of the invention is not believed to be critical, so long as it is capable of expressing the polynucleotide in a targeted cell, preferably a bacterial cell. Where a mammalian cell is targeted, it is preferable to position the polynucleotide coding region adjacent to and under the control of a promoter that is capable of being expressed in a mammalian cell. Generally speaking, such a promoter might include either a bacterial, human or viral promoter.

[0273] In various embodiments, the human cytomegalovirus (CMV) immediate early gene promoter, the SV40 early promoter, and the Rous sarcoma virus long terminal repeat can be used to obtain high level expression of a related polynucleotide to this invention. The use of other viral or mammalian cellular or bacterial phage promoters, which are well known in the art, to achieve expression of polynucleotides is contemplated as well.

[0274] A specific initiation signal also may be required for efficient translation of coding sequences. These signals include the ATG initiation codon or adjacent sequences. Exogenous translational control signals, including the ATG initiation codon, may need to be provided. One of ordinary skill in the art would readily be capable of determining this and providing the necessary signals. It is well known that the initiation codon must be "in-frame" with the reading frame of the desired coding sequence to ensure translation of the entire insert. The exogenous translational control signals and initiation codons can be either natural or synthetic and may be operable in bacteria or mammalian cells. The efficiency of expression may be enhanced by the inclusion of appropriate transcription enhancer elements.

[0275] In certain embodiments of the invention, the use of internal ribosome entry sites (IRES) elements are used to create multigene, or polycistronic, messages. IRES elements are able to bypass the ribosome scanning model of 5' methylated Cap dependent translation and begin translation at internal sites. IRES elements from two members of the picornavirus family (polio and encephalomyocarditis) have been described, as well an IRES from a mammalian message. IRES elements can be linked to heterologous open reading frames. Multiple open reading frames can be transcribed together, each separated by an IRES, creating polycistronic messages. By virtue of the IRES element, each open reading frame is accessible to ribosomes for efficient translation. Multiple genes can be efficiently expressed using a single promoter/enhancer to transcribe a single message (see U.S. Pat. Nos. 5,925,565 and 5,935,819, herein incorporated by reference).

[0276] 2. Multiple Cloning Sites

[0277] Vectors can include a multiple cloning site (MCS), which is a nucleic acid region that contains multiple restriction enzyme sites, any of which can be used in conjunction with standard recombinant technology to digest the vector. Frequently, a vector is linearized or fragmented using a restriction enzyme that cuts within the MCS to enable exogenous sequences to be ligated to the vector. Techniques involving restriction enzymes and ligation reactions are well known to those of skill in the art of recombinant technology.

[0278] 3. Splicing Sites

[0279] Most transcribed eukaryotic RNA molecules will undergo RNA splicing to remove introns from the primary transcripts. If relevant in the context of vectors of the present invention, vectors containing genomic eukaryotic sequences may require donor and/or acceptor splicing sites to ensure proper processing of the transcript for protein expression.

[0280] 4. Termination Signals

[0281] The vectors or constructs of the present invention will generally comprise at least one termination signal. A "termination signal" or "terminator" is comprised of the DNA sequences involved in specific termination of an RNA transcript by an RNA polymerase. Thus, in certain embodiments a termination signal that ends the production of an RNA transcript is contemplated. A terminator may be necessary in vivo to achieve desirable message levels.

[0282] In eukaryotic systems, the terminator region may also comprise specific DNA sequences that permit site-specific cleavage of the new transcript so as to expose a polyadenylation site. This signals a specialized endogenous polymerase to add a stretch of about 200 A residues (poly A) to the 3' end of the transcript. RNA molecules modified with this polyA tail appear to more stable and are translated more efficiently. Thus, in other embodiments involving eukaryotic cells, it is preferred that that terminator comprises a signal for the cleavage of the RNA, and it is more preferred that the terminator signal promotes polyadenylation of the message.

[0283] Terminators contemplated for use in the invention include any known terminator of transcription described herein or known to one of ordinary skill in the art, including but not limited to, for example, the bovine growth hormone terminator or viral termination sequences, such as the SV40 terminator. In certain embodiments, the termination signal may be a lack of transcribable or translatable sequence, such as due to a sequence truncation.

[0284] 5. Polyadenylation Signals

[0285] In expression, particularly eukaryotic expression, one will typically include a polyadenylation signal to effect proper polyadenylation of the transcript. The nature of the polyadenylation signal is not believed to be crucial to the successful practice of the invention, and/or any such sequence may be employed. Preferred embodiments include the SV40 polyadenylation signal and/or the bovine growth hormone polyadenylation signal, convenient and/or known to function well in various target cells. Polyadenylation may increase the stability of the transcript or may facilitate cytoplasmic transport.

[0286] 6. Origins of Replication

[0287] In order to propagate a vector in a host cell, it may contain one or more origins of replication sites (often termed "on"), which is a specific nucleic acid sequence at which replication is initiated. Alternatively an autonomously replicating sequence (ARS) can be employed if the host cell is yeast.

[0288] 7. Selectable and Screenable Markers

[0289] In certain embodiments of the invention, cells containing a nucleic acid of the present invention may be identified in vitro or in vivo by encoding a screenable or selectable marker in the expression vector. When transcribed and translated, a marker confers an identifiable change to the cell permitting easy identification of cells containing the expression vector. Generally, a selectable marker is one that confers a property that allows for selection. A positive selectable marker is one in which the presence of the marker allows for its selection, while a negative selectable marker is one in which its presence prevents its selection. An example of a positive selectable marker is a drug resistance marker.

[0290] Usually the inclusion of a drug selection marker aids in the cloning and identification of transformants, for example, markers that confer resistance to neomycin, puromycin, hygromycin, DHFR, GPT, zeocin or histidinol are useful selectable markers. In addition to markers conferring a phenotype that allows for the discrimination of transformants based on the implementation of conditions, other types of markers including screenable markers such as GFP for colorimetric analysis. Alternatively, screenable enzymes such as herpes simplex virus thymidine kinase (tk) or chloramphenicol acetyltransferase (CAT) may be utilized. One of skill in the art would also know how to employ immunologic markers that can be used in conjunction with FACS analysis. The marker used is not believed to be important, so long as it is capable of being expressed simultaneously with the nucleic acid encoding a protein of the invention. Further examples of selectable and screenable markers are well known to one of skill in the art.

[0291] The eleventh aspect of the invention relates to a cell which is transformed so as to carry the vector of the invention--particularly preferred transformed cells are also capable of expressing the nucleic acid fragment of the invention in order to enable production of the polypeptides disclosed herein.

[0292] The transformed cell may hence be capable of replicating the nucleic acid fragment defined in option i) or ii) of the ninth aspect of the invention and/or capable of expressing said nucleic acid fragment.

[0293] Depending on the particular use of the transformed cell it can be of prokaryotic or eukaryotic origin cell. Preferred prokaryotic cells are bacteria selected from the group consisting of Escherichia (such as E. coli.), Bacillus (e.g. Bacillus subtilis), Salmonella, and Mycobacterium, preferably non-pathogenic, e.g. M. bovis BCG. Preferred eukaryotic cells are fungal cells, insect cells, mammalian cells, and plant cells.

[0294] For production purposes, it is preferred that the cell is stably transformed by having the nucleic acid defined in option i) or ii) of the ninth aspect of the invention stably integrated into its genome.

[0295] Also for production purposes, it is preferred that the transformed cell secretes or carries on its surface the polypeptide disclosed herein--when the cell is a bacterium, it may be advantageous that secretion is into the periplasmic space or into the culture medium.

[0296] The twelfth aspect of the invention is a cell line derived from a transformed cell of the invention. In particular clonal cell lines are interesting.

[0297] The twelfth aspect of the invention relates to a method for the preparation of the polypeptide disclosed herein, comprising

[0298] culturing a transformed cell or cell line of the invention under conditions that facilitate that the transformed cell expresses the nucleic acid fragment according to option i) of the ninth aspect of the invention and subsequently recovering said polypeptide, or

[0299] preparing said polypeptide by means of solid or liquid phase peptide synthesis.

[0300] The twelfth aspect may be preceded by steps that include recombinant preparation of the cell or cell line of the invention, i.e. introduction of a vector of the invention into a host cell and propagation and selection of those transformed cells that effectively express the nucleic acid of the invention.

[0301] The thirteenth aspect of the invention relates to antibodies that specifically bind and recognize a polypeptide of the first aspect of the invention, in particular the polypeptides having the amino acid sequences set forth in SEQ ID NO: 1-44 and 261-332 (preferably SEQ ID NOs: 1-44 and 305-318).

[0302] As such, the antibody may be an isolated polyclonal antibody, which has been raised against the polypeptide of the first aspect of the invention. In this connection "isolated" is intended to mean that the polyclonal antibody is essentially free from antibody species that bind non-specifically to the polypeptide of the first aspect. Another way to phrase this is that the polyclonal antibody of the present invention is essentially free from antibody species that have K.sub.D values >10.sup.-6 for binding to the polypeptide of the first aspect of the invention.

[0303] Polyclonal antibodies of the invention can be obtained from any mammalian species of convenience: the antibody can e.g. be isolated from a rabbit, mouse, rat, cat, dog, horse, cow, camel, llama, or even a human being.

[0304] Also, the antibody can be a monoclonal antibody or a fragment or analogue thereof, which specifically binds the polypeptide of the first aspect of the invention.

[0305] A "fragment or analogue" of a monoclonal antibody comprises at least the antigen-binding or variable regions of the monoclonal antibody. Examples of antibody fragments/analogues include Fab, Fab', F(ab).sub.2, F(ab').sub.2, F(ab).sub.3, Fv (typically the VL and VH domains of a single arm of an antibody), single-chain Fv (scFv), dsFv, Fd fragments (typically the VH and CH1 domain), and dAb (typically a VH domain) fragments; VH, VL, VhH, and V-NAR domains; minibodies, diabodies, triabodies, tetrabodies, and kappa bodies (see, e.g., Ill et al., Protein Eng 1997; 10: 949-57); camel or llama IgG; IgNAR; and multispecific antibody fragments formed from antibody fragments, and one or more isolated CDRs or a functional paratope, where isolated CDRs or antigen-binding residues or polypeptides can be associated or linked together so as to form a functional antibody fragment. Various types of antibody fragments have been described or reviewed in, e.g., Holliger and Hudson, Nat Biotechnol 2005; 23, 1126-1136; WO 2005/040219, and published U.S. Patent Applications 2005/0238646 and 2002/0161201, all of which are incorporated by reference herein.

[0306] The monoclonal antibody of the invention, the fragment, or the analogue thereof may also be presented in the form of a "derivative", wherein one or more of the amino acids of the monoclonal antibody, the fragment, or the analogue are chemically modified, e.g., by alkylation, PEGylation, acylation, ester formation or amide formation or the like, e.g., for linking the antibody to a second molecule. This includes, but is not limited to, PEGylated antibodies, cysteine-PEGylated antibodies, and variants thereof.

[0307] Monoclonal antibody are preferably those having high affinity for the polypeptide of the first aspect of the present invention. Typically, high affinities, expressed as a K.sub.D of less than 10.sup.-6 are preferred, and even lower K.sub.D values are preferred, such as less than 10.sup.-7, 10.sup.-8, 10.sup.-9, 10.sup.-10, 10.sup.-11, or 10.sup.-12.

[0308] The fourteenth aspect of the invention relates to methods of detecting, quantitatively or qualitatively, the presence in a sample of a polypeptide of the first aspect of the present invention. For example, the sample may be an allergen extract or an immunotherapy product comprising an allergen extract or a polypeptide of the first aspect. The method may be performed in order to characterise an allergen extract, either qualitatively or quantitatively. Any convenient detection method may be employed. For instance, many such methods (which are by nature qualitative or semi-quantitative) rely on the use of specifically binding antibodies. For instance, detection may entail contacting the sample with an antibody of the thirteenth aspect of the invention and detecting specific binding of material in said sample to said antibody. Such assays may have very simple formats and can e.g. be in the form of agglutination assays or immunoblots (dot blot analysis, quantitative dot blot, Western blot) of any format. To facilitate detection the antibody may be labelled with a radioactive isotope, a component of a ligand/receptor pair, a luminescent or fluorescent label, an enzyme, etc.

[0309] Possible formats for use in immune detection are for instance

[0310] contacting the sample with a system comprising a solid phase with an antibody of the thirteenth aspect coupled thereto and comprising a labelled polypeptide (as described above) of the first aspect of the invention, where said labelled polypeptide specifically binds said antibody, and gauging the degree of competition exerted by material in the sample on the binding between said labelled polypeptide and said antibody; hence, this format is in the form of a competitive binding assay where the ability of the sample to out-compete a polypeptide of the first aspect is gauged,

[0311] contacting the sample with a system comprising 1) a solid phase with a polypeptide of the first aspect coupled thereto and comprising 2) a labelled antibody of the thirteenth aspect, where said polypeptide specifically binds said labelled antibody, and gauging the degree of competition exerted by material in the sample on the binding between said polypeptide and said antibody; also this is a competitive assay, but here the ability of the sample to attract labelled antibody is gauged.

[0312] The latter immune assays may be put into practice in a number of format known per se in the art: ELISAs, RIAs, etc.

[0313] A further possibility is to utilise the polypeptides of the first aspect in similar assay formats but with a view to identifying IgE antibodies in a sample. In such assays (e.g. RAST assays), possible presence of anti-polypeptide IgE is gauged by either indirect assays (competitive assays) or in assays that determine direct binding between polypeptide and antibody.

[0314] A further embodiment of the method of the fourteenth aspect of the invention relates to mass spectrometric identification or quantification of a polypeptide of the first aspect of the invention in a sample, for example in an allergen extract or an immunotherapeutic product comprising an allergen extract or a polypeptide of the first aspect. In essences, the polypeptide material of a sample is subjected to proteolytic treatment and the thus obtained material is subsequently subjected to quantitative MS, optionally using at least one polypeptide of the first aspect or a fragment of said polypeptide, which is obtainable by the same proteolytic treatment as the sample, but often produced synthetically. Thus, a further embodiment of the invention relates to a synthetically produced fragment of a polypeptide of the first aspect, which is identical to a fragment produced by proteolytic treatment of said polypeptide. Proteolytic treatment may be performed with trypsin or chymotrypsin or other enzymes known in the art. The synthetically produced fragment may be used in the mass spectrometric identification or quantification of said polypeptides. This method is in particular useful if the polypeptide tested has any one of SEQ ID NO: 1-44, and 261-332, but in particular of the naturally occurring polypeptides having SEQ ID NOs: 1-44 and 305-318.

[0315] Methods for qualitative determination for instance involve mass fingerprinting methods as those taught in Trauger A. et al. (2002), Spectroscopy. 16 (1): 15-28. For relevant teachings pertaining to quantitative determination, reference is made to Wells W et al. (2006), Journal of Proteome Research. 5 (3): 651-658, as well as to Bret, Cooper and J. Feng and W. Garrett (2010), Spectroscopy. 21 (9): 1534-1546, Haqqani A S et al. (2008), Methods Mol. Biol. 439: 241-56. These references are incorporated by reference herein.

[0316] If employing labelling of standard peptides for use in qMS, SILAC (stable isotope labeling by amino acids in cell culture), trypsin-catalyzed .sup.18O labelling, ICAT (isotope coded affinity tagging), and iTRAQ (isobaric tags for relative and absolute quantitation) are useful. "Semi-quantitative" mass spectrometry may be performed without labelling of samples, e.g. with MALDI analysis (in linear mode). The peak intensity, or the peak area, from individual proteins is correlated to the total amount of protein in the sample. Other types of "label-free" quantitative mass spectrometry uses the spectral counts (or peptide counts) of enzyme digested proteins as a means for determining relative protein amounts.

[0317] It is however preferred to employ labelled standard peptides in the qMS methods. Reference is generally made to the quantification methods taught in WO 2007/031080.

[0318] Sequences

[0319] The amino acid sequences of the polypeptides of the present invention are set forth in the sequence listing. For ease of reference, the sequences are provided as follows, together with the alternative designation used herein as well as their origin.

TABLE-US-00001 SEQ ID NO: 13; Cluster ID (L) 96; Cluster ID (A) 55 Protein name: A0001; Species: Dermatophagoides farinae KKTKDCDVEK PIRECLKNGL LRYSDGQKIN QFPDSIEDLN RACEELKKSE TCARNFIDTC TETSYEKRSL DSLLDGIQRV LKRLCRSQSK KEQLLQNVGC ANSVVQDTKL CLKNYRMLVF AANKLNDKSK IMRILCCKSR KVAPCIGEAM KSKGNAVCSA KNIDYFREMH QNIKAEMTAV VCSDFERDQC ENVEVPAITE AEYKDQNIFN PLRDLYKKVI LA SEQ ID NO: 14; Cluster ID (L) 96; Cluster ID (A) 55 Protein name: A0001; Species: Dermatophagoides pteronyssinus KKSPDCDIER PIRECLKDGL LRYSSGQKIN QFPDTIQDLN RACEELKKSE TCARTFIDTC TESSYEKRSL DSLLDGIQRV MKRLCRSQTK KEKLLENVGC ANSVVQDTKQ CLKNYRMLVF AANKLDNKNK IMRILCCKSR KVAPCIGEAM KAKGTAVCSA KNIDYFKDVH QNIKQEMTAV VCSDFERDQC ENVDVPNISE SEYKDQNIFN PLRDLYKKVI LG SEQ ID NO: 2; Cluster ID (L) 65; Cluster ID (A) 74 Protein name: A0003; Species: Dermatophagoides farinae MAIDGKYQME SSEHFEEFVK EMGLDVDMTN VDLSKTSTME ICKDGDVYHI KSETAGIAHE IKFKVGEEFE DDMNGHKFKN VVTMECDNKM VQKKTSADGG KVVNVVREFT DAGCTVKSTY NTVTWTRVYK RM SEQ ID NO: 3; Cluster ID (L) 65; Cluster ID (A) 74 Protein name: A0003; Species: Dermatophagoides pteronyssinus MAIDGKYQME SSEHFEEFVK EMGLDVDMTN VDLSKTSTME ICKDGDVYHI KSETAGIAHE IKFKVGEEFE DDMNGHKFKN VVTMECDNKM VQKKTSADGG KVVNVVREFT DAGCTVKSTY NTVTWTRVYK RM SEQ ID NO: 305 Protein name: A0003; Species: Blomia tropicalis GKYQLESSEN FDEFLKELGV NFILRNLAKT SKPTIEITLD GDTYTIKTIT TLKTSVITFK IGEEFEESRM DGKTVKTVIT QEGDKLIQVQ QGDKEVKIVR EFTETHLTTI CTVGEITSTR VYKRV SEQ ID NO: 34; Cluster ID (L) 46; Cluster ID (A) 21 Protein name: A0006; Species: Dermatophagoides farinae DSNSDTTFIF NGDGCEQNHL FQTRYRPQIQ QLASDVQRII DHVMSVNESG RTYRQLAEFV DRFGSRLTGT KNLEDSIDYM IDLLRQEGHD NVHGESVQVP RWTRGNEWAR MIKPREKKLN ILGLGYSEGT NGQTIEAPIV VVRNFTELEQ KSRLIPGKIV VYNFHYESYG KQAIYRHSGA SRAAEFGAVA AMIRSLTPFS IDSPHTGMQT YDVNVTRIPA ISITAEDADL FQRFSDRNEE VIVQIYSENR NEKEQGISPN TVSDIRGEQY PDEIVLVSGH IDSWDVGQGA LDDGAGSFIS WRALSVIKQL GLRPKRTMRS ILWTGEEFGL IGVYDYVKKH QNELKNYVLA MESDIGTFTP KGITFSGRNS TSQCTLWEIL QLMHPINATT LTISTEGSDV QAFYENGVPI SSLDTANDKY FYFHHTQGDT MTVEQSDDLD KCQALWTSIS YALAMLDDRL PR SEQ ID NO: 35; Cluster ID (L) 46; Cluster ID (A) 21 Protein name: A0006; Species: Dermatophagoides pteronyssinus DSNPGETSIF NGEGCANDQL FQTRIRPQIQ QLASNVQRII DHVMSANESG RTYRQLAEFV DRFGSRLTGT KNLEDSIDYM IDLLKQEGHD NVHGEPVQVP KWTRGNEWAR MIKPRDKKLN ILGLGYSEGT NGQTIEAPIV VVRNFTELEQ KAGLIPGKIV VYNFKYESYG KQAIYRHSGA SRAAKFGAVA AMIRSLTPFS IDSPHTGMQS YDVNVTKIPA ISITTEDADL FQRFSDRNEE VIVQIYSENH NEKDKGISPN TVSDVRGEKY PNEIVLVSGH IDSWDVGQGA SDDGAGAFIS WRALSVIKKL GLRPKRTLRS VLWTGEEFGL IGVYDYIKKH RNELKDYVIA MESDIGTFTP RGITYSGKNS TSQCTLWEIL QLMHPINATT LTISTEGSDV QAFYENGVPI SSLDTANDKY FYFHHTQGDT MTVEQPDDLD KCQALWTSVS YALAMLDDRL SR SEQ ID NO: 30; Cluster ID (L) 61; Cluster ID (A) 30 Protein name: A0007; Species: Dermatophagoides farinae MAKFNYLPVD VQEELPNTAN AIVSVGKGIL AADESTGTIG KRFADINVEN VEPNRRAYRQ LLFYSENIEQ YISGVILFDE TVYQKDDNNT PFPELLKKKG IIPGIKVDTG VVTLQGTNGE STTQGLDNLT KRCQEYYNHG CRFAKWRCVL KIGKDEPSAL AILENANVLA RYASCCQQAR IVPIVEPEIL PDGDHDLERC QKVTETVLAA VYKALNDHHV YLEGSLLKPN MVTPGQSCPQ KASPQDIARA TVTALQRTVP AAVPGVVFLS GGQSEEEASV NLNAINQYQG KKPWALSFSY GRALQASALR AWQGKPENIS AGQKEFLQRA KANSLSAQGQ YTGGVVGAAA DQDLFIKDHQ Y SEQ ID NO: 31; Cluster ID (L) 61; Cluster ID (A) 30 Protein name: A0007; Species: Dermatophagoides pteronyssinus MAKFNYLPVD VQEELPNTAN AIVSVGKGIL AADESTGTIG KRFADINVEN VEQNRQAYRQ LLFYSEGIEQ YISGVILFDE TVYQKDDKGV PFPELLKKKG IIPGIKVDTG VVTLQGTNGE STTQGLDNLT KRCQEYYNQG CRFAKWRCVL KIGQDEPSSL AIVENANVLA RYASCCQQAR IVPIVEPEIL PDGDHNLERC QKVTETVLAA VYKALNDHHV YLEGTLLKPN MVTPGQSCPQ KASPQEVAQA TVTALQRTVP AAVPGIVFLS GGQSEEEASV NLNAINQYQG KKPWALSFSY GRALQASALR AWQGKPENIG AGQKELLQRA KANVLAHKGQ YVAGSIPSLA SAKSNFVAQH KY SEQ ID NO: 306 Protein name: A0007; Species: Blomia tropicalis MSIIQNLPAD VQEELRKTAN AIVTPGKGIL AADESTGTIG KRFADINVEN VENNRRTYRD LLFSAPDEVN NYISGVILFD ETVYQKNAAG VPFPQVLAKR GIIPGIKVDT GVVVLQGTNG ESTTQGLDNL TKRCQAYYEQ GCRFAKWRCV LKIGDNEPSP LAILENANVL ARYASCCQQA RIVPIVEPEI LPDGAHDIER CQKVTEKVLA AVYKALNDHN VFLEGTLLKP NMVTAGQSFA GPKPSPQEVA RATVTALQRT VPAAVPGIVF LSGGQSEEEA SINLNAINQF EGKKPWALSF SYGRALQASV LRAWQGKDEL IAAGQKELVN RSKANSDASL GKYSGGIVGA AGEQDLFIKD HQY SEQ ID NO: 7; Cluster ID (L) 44; Cluster ID (A) 67 Protein name: A0008; Species: Dermatophagoides farinae MSANTERTFI MLKPDAVQRG IVGEIIRRFE AKGFKLVAMK FMMASEDLLK KHYADLAARP FFPGLIKYMQ MGPVVPMVWE GLNAVKTGRV MLGETNPAES KPGTIRGDLC IQTGRNIIHG SDSVETAKRE IDLWFRPEEL VDYKPSQYEW VYEN SEQ ID NO: 8; Cluster ID (L) 44; Cluster ID (A) 67 Protein name: A0008; Species: Dermatophagoides pteronyssinus MSANTERTFI MLKPDAVQRG IVGEIIRRFE AKGFKLVAMK FMMASEDLLK KHYADLAARP FFPGLIKYMQ MGPVVPMVWE GLNAVKTGRV MLGETNPAES KPGTIRGDLC IQTGRNIIHG SDSVETAKRE IDLWFRPEEL VNYKPSQYEW VYEN SEQ ID NO: 43; Cluster ID (L) 58; Cluster ID (A) 6 Protein name: A0009; Species: Dermatophagoides farinae VVIKVENLPE RCDYSQCPKW DPNDINVHLV AHTHDDVGWL KTVEQYYYGL KNDIQRAGVQ YILDTVIEEL IRNKQRRFIY VEIAFFWKWW QEQDEDQRMI VRELVRTGQL EFINGGWSMP DEAATHYNSL IDQSTWGLRQ LNDTFGKCGH PKVTWQIDPF GHSREMANLY AQMGYDALFF ARQDYQDREN RMTNRKLEHV WQGSDDLGTA GDIFTGMMFS GYGPIEFNWD ITNGPEDAVV DNPESEEYNV PDKIRRFVEK AKYFAQYYAT NHFMFPMGTD FQYGDAHTWF KNLDKLIKAV NNAGKGVRAF YSTPSCYARA LYETNRTWTT KTDDFFPYAS DEHAYWTGYF TSRPALKRME RMGNNLLQAC KQLDILAGND GRFEMNITRL REAMGVMQHH DAVTGTEKQH VAFNYAKMLD SAMLQCRHVI SESYRKLFPT QTKEQHEFCP YLNISSCPST EMGESRTIHL YNPLGHRLVN RTIRVPVKDG YYYQVRDQND HSIPAVLISI PEFVRKIPGR KSVATKELVF RVPIIESLGI RRFHMIATKE KQQDSAVEIQ GEKFVGHKGQ RFQLKDGLII EFDSNGKIAT MIRNNQSISI SNEFRLFHGA DIGRHSGAYI FRPSEQKTFP VTEKMEATLY VDQKFGIVQE VHQQFDSFVG QIIRLDKQGD YVEFDFVVGP IPVDDLIGKE IITRYNTNLA NDETFFTDSN GRQMLRRRWN YRPSWKYEIE EPVSGNYYPV NSRIAIRDDR KSLQMTIMTD RSQGGSLSPE QINGSVDLMV HRRLLHDDYF GVDEPLNEPG VDGHGIVIRG RHLLLLDTLE KAAEKHRPLA QEMFMEPIIS FTSSMEKNQP IYKGLTKDLP GNVHLLTLEQ WHSKRYLLRL EHFYQRFEDP SLSNPATVSL RHLFQSFEIT AVEELTLGAN QPISALKNRL QYRYIRPLNE QQSSIITDPI IEGENFDIHL EPMQIRTFLI DIKRN SEQ ID NO: 44; Cluster ID (L) 58; Cluster ID (A) 6 Protein name: A0009; Species: Dermatophagoides pteronyssinus VVIKVENLPE QCDYTQCPKW SKDDINVHLV AHTHDDVGWL KTVEQYYYGL KNDIQRAGVQ YILDTMIEEL IRNKDRRFIY VEIAFFWKWW QEQNEEQRMI VKELVRTGQL EFINGGWSMP DEAATHYNSL IDQSTWGLRQ LNDTFGRCGH PKVTWQIDPF GHSKEMANLY AQMGYDALFF ARQDYQDREN RMSNRTLEHV WQGSDDLGEI GDIFTGMMFS GYGPIEFNWD ITNGPEDAVV DNPESEEYNV PDKIRRFVEK AKYFGQFYAT NHFMFPMGTD FQYTDAHTWF KNLDKLINAV NKAGKGVRAF YSTPSCYAEA LYEQNRTWTT KTDDFFPYAS DEHAYWTGYF TSRPAIKRME RIGNNLLQAC KQLDVLADNN GRFEMNLTKM REAMGVMQHH DAVTGTEKQH VAFNYAKMLD SAMLQCRHII NESYKKLLPK SSTSEHEFCP YLNISSCPTT EMGESRIIYL YNPLGHRLIN HTVRLPIKNG YYYRIQDQNN QSVPSVLVPI PEFVQKIPGR KSVATKELVF RVPVIEPLGI TTMYMYVDKN EQPNSAIEIK GENPDDNDDK SKWLVLTKNL IVEFYSNGTI SRISIDKLHQ SISISNEFRL YHGAGGTGRH SGAYIFRPNE QKTFPVTNKI KSTFFIDRKY HIVQEVHQQF DSSFVGQIIR MDKYNDNVEF DFVVGPIPVN DQIGKEIIAS YKTDLENDET FYTDANGRQM LRRRWNYRPS WKYNVQEPIS GNYYPVNSRI AIRDEKQSLQ MTIMTDRSQG GSLSPEQING SIDIMIHRRL LHDDYFGVGE ALNEPGVDGH GLVIRGKHLL LLNSIKQSAS EHRPLAQQMF MEPIISFTSI ESNKQAEKQS NQYIGLNNDL PSNVHLLTLE QWHSKRYLLR LEHFYQSNED TELSKPVKLS LRHLFKSFEI IAVEELTLGA NQPISSLKNR LHYRYNRPLE QRQQQQSSLL LDDPKIEGEN FDIHLSPMQI RTFLIDIKPN SEQ ID NO: 307 Protein name: A0009; Species: Blomia tropicalis VVIKVENLPA RCDYTKCPKS DPNKINVHLV PHTHDDVGWL KTVEQYYYGS KTYYQKAGVQ YILDSVMNEL IHNKERKFIY VETAFFWKWW MEQDYGMRNI VKELVETGQL EFINAGWSMN DEASTHYNSI IDQMSWGFYR LQTTFGRCGV PKVAWQIDPF GHSKEQAALF ALMNFDALFF AREDWQEQSH RRKNRTLEHV WQASSDLGKS ADLFTGMMNF GYGPPQGFNW DLVGGADEPV IDDPESDEYN VPRRVKELID LAKTYQKYYA TNNVMFPMGT DFQYQDAHIY FKNMDKLIKY VNENSTEVNI FYSTPSCYAK SLKDSGKTFT AKNDDYFPYA SDPHSYWTGY FTSRPAIKRF ERVGNNYLQV CKQMDTYTGH QATRDRHTTK LREIMGVMQH HDAVSGTEKQ HVAFNYAKHL QSGIESCRKV ISEAYQLLQH PHTKTVQTFC DYLNISSCAI TESGQNFVVN IYNPLSKTLK NHPIRLPINS DKYYNVVDDE GKSVYSELTF IPEYVQAIPE RTTNATTDLV FLASIPPLGY ASYFVQATTT KSPDSANAVT VTKITNETRL SSGNFSVVFD STGALSKVEL PSGESIPFKN EFRYYNGAAD NIRASGAYIF RPKEQQTFPF AKLVSANLLT RTSSGGIVHE VHQKFDSNVE QVIRVLPDSD SIEFEYVVGP IPVKDGIGKE VVLTYETDFK NNKTFYTDAN GRQMMKRKWD YRPEFKMEVT EPISGNYYPI NSRIYLQDEK KGMQMTILND RSQGGTSPRD GVIEIMVHRR LLHDDGFGVG EALNEPGVDN KGLIIRGRHL VQFSDIKTAA SKHRPKAQQL FMAPVLSFVP DVSDYETYKR SHLTKYSALI NPLPEQIHLL TLERWMEGHF LLRLEHYFQT NEDAELSKPV TLNLKHMFKS FKIFEAEELT LGGNQPIFET KHRMKFNYIP VENVTEPPEH SFDPTKLEVK LYPMQIRTFS VRV SEQ ID NO: 41; Cluster ID (L) 10; Cluster ID (A) 7 Protein name: A0010; Species: Dermatophagoides pteronyssinus LDSDPMKCNS IPNEDRIDCN PDPPISKEIC EQRGCCWNAG NNTDDGNLIS RALPHLGVPS CYYGENYIGY KIEKIYIKDE DLSMTKLKRV RPSGFPKDIE NVNIEIHQLN DQVLRLKFID ANQKRYEVPT PKLNIPSVSK SSNSRLYSTE ISGSHLIVRR RETNQSIFDI NLAQMVYSDQ LIHLTSKLPS KYIYGIGEHR EPFRKTTDWK RYTQWTRDQV PISDHALYGS HPFYMMVENK TKLASGVFLF NSNAMDILTQ PSPAITFRTV GGILDFFIFF GPKPEQVVQQ YHNLIGLPAM PPFWSLGYQQ CRYGYNNFTN LNQTYWRTRQ AGIPMDVQWT DIDMFDSYND FTYNHKQFKE LPDFIRNVLH KNGQKFIPMF DCGISSGEKA HSYRPYDYGV ELDIFVKNSS KQIFNGKVWN GKSTVWPDFS HPNATKYWSK MFEEYHKIIE FDGAWIDMNE PSNFYDGQID GCPKTEIENP QYVPGMTDDS LTLRHKTLCM TARHYNDQLH YNLHNLYGFQ EAIATNEALK TTLNKRPFII SRSSAPGHGH WASHWDGDVI SDWSSMRWTI PSILNFNLFG VPMIGADICG FNGDTTVELC RRWYQLGAFY SFVRNHNTDN AIDQDPVALG ETVVRTARSA LTYRYAFLPY LYTLFYNVHQ NGGTVLRPMF FEFPDDDHLY DIETQFMWGD SMLIAPILYP NQTENKVYLP KGTWHNMRQT FESQGQYFTI KDSLDDINYV FFRSGSIIPI QGPQNNTEMM KSKDFGLVVI LDSKNPEPYA KGSLYLDSGD SLDPVKKGEY NFYNFEVKNN TLTIESQHLG YQTNQSIIIL EILGIDRKPT SIIFDGKPYY QFIYTTNNML IIQTKLSIFN DNDKSKKIHY QFEWKFN SEQ ID NO: 42; Cluster ID (L) 10; Cluster ID (A) 7

Protein name: A0010; Species: Dermatophagoides farinae DSLKCSSIRN EDRIDCNPDP PISKNVCEQR GCCWKTAGND LKNLSSKVLP NLNVPYCYYG ENYIGYKIEK HSKNLIQLKR NRSSGFARDI ENINIEIHEL NDKVIRLKFI DANKKRYEVP IPKLNLPSTT SSSSSNSRLY SVELDGSHLI VRRRETNQSI FDINLAYMVY SDQLIHVTSR LPSKYIYGLG EHRAPFRKNT NWKRYTQWTR DQYPVTDKAL YGNHPFYLTV EDESPKKSAS GVFLFNSNAM DIITQPSPAI TFRTIGGILD FFVFFGPKPE DVISQYQNLI GLPAMPPFWS LGYQQCRYGY NNFTNLNTTY TRNRAVGIPM DVQWTDIDAF NSNNDFTYDH KRFKELPDFI NNVLHPNGQK FIPMFDCGIS SGEPAGSYKP FDSGVELDVF VKNSSNKIFR GKVWNGKSTV WPDFSHPNAT EYWMDMFAEY HKTIAFDGAW LDMNEPSNFY NGEEHGCPES EIENPQYVPG MTDDSLTLRH KTLCMTARHY NDQLHYNLHN LYSLSMAMAT NAALTKLNKR PFIISRATAP GHGHWAYHWN GDILSDWSSM RWTIPSILNF NMFGIPMVGA DICGFGGNTA EELCIRWYQL GAFYSFARNH NDIHSIDQDP AALGESVIRA ARSSLQYRYR FLAHLYTLFY HVHKNGGTVL RPMFFEFPHD EHTYEIETQF MWGDSVLIAP ILYPNQTQHK IYLPKGTWYN RKVSFESQGQ YITMNDSYDD IDYVFVRGGS IIPTQEPHDN TELMKTKDFL LIVALDNQTS YAKGSLYWDS GDSLNPDKTG HYNFYNFDAV NNTLTIQSQW LGYQTTQNIN FINILGVPKL PTSFKLNGHV SDPRIIRFNY DEQTNILTVE TKLPIYNQDS SSHDRIHYQF EWIME SEQ ID NO: 308 Protein name: A0010; Species: Blomia tropicalis QCMAIPPNSR IDCNPDPPIS AEVCQSRGCC WMPSSNESSE NMNLLKKNVL PPLNVPYCFF GSDYHGYNVS NVQTINDNQK VINLQRIRDS GFVNDVKNVR IQIDELSSNV LRIKMIDSDS SRYEVPIPVL NLPKRNEVLE SLNEKMYQVE MNSTDFMLTV YRAKTKAIVF NVNLGQLIYS NQFIQITNKL ASNFIFGIGE NRESFRKLTN WKRYTLFARD QWPVPDRALY GSHPFYLATE SDNSSHGVFL FNSNAMDIIT QPMPAITYRT IGGILDFFLF LGPTSENVIE QYHQLIGLPT MPAYWTLGFH LSRYGYRNLS NLEKTFRRTR KAEIPFDVQW TDIDMFDSNN DFTYDRKRFD GLPKFIEHLH SINMRFVPMF DCGISSGEHP PQSYLPYKMG LEMNVFVRNG TNQPFEGKVW NSKSTVWPDF THPNATKYWT RQFAEYHKTI QFDGAWIDMN EPSNFLDGAF NGCPTNSTLE TPQYTPGMVE DSLTLNHKTL CMSARHSIGL HYNLHNLYGI SEAIVTKSAL ESVLKRRSFI LSRSTAPGHG HFAAHWDGDI LSDWPSMKWS ISSILNFNIF GVPLIGADIC GFNGNTTIEL CARWHQLGAF YTFVRNHNTD NAIDQDPVAL GPLVVKAAKN ALKLRYALLP YLYTQFYRVH RKGGTILRPL FFEFVHDQVV LEIETQFMWG SSIMVAPALS INETETSVYF PSGTWFHSYN FTRINTIGKF LPQLASFDYP NVYFRAGSII PTLRPMLTTD ETHSGNFTLL VALSNENGHA EGDLYLDSGD GLDTEVLGHY NLYSFKVEKK ILEIKSSHLG YSTEQMIDNV LILGIDKSPI EIKINGRSMK SWSYSKNKIH INSLNLPLYD LKTIDKSKLI QIHYQIEWV SEQ ID NO: 39; Cluster ID (L) 64; Cluster ID (A) 16 Protein name: A0011; Species: Dermatophagoides farinae KKAPEGCFRA AVLDHVHQTN VRQLSDFAKI IELNFKVYED AAALAKKQGA DIIVFPEDGL IYNIASREKA DEFASDIPDG ETNACTLETK SVYNRLACLA QKHEIFVVAD LIDRKSCEEL GISNTSDSCP ADKKFLFNTA VLFDRQGKLL GRYHKMHLFG EMTMNIPPKP ELLVIDTELG RLGMQICFDM IFKTPGHFLA EQNKFDTMLF PTWWFDEAPM LSSSQYQMAW AFGNNVTLLA SNIHRVELGS RGSGIYVGPH QTLATALYDD SVERLVLANV PIKPRETDKS VCPLDSEIIE VPQQIPIPNS VKYHHLNMNL LDVTLVELSS KDSEFHICYK GVCCQIEYRL AVKDQPRESW VDRVPLLANM LEYFTPEERY YLMVANRTRP GTYRWTEEIC AVVVCPSSRW NIGKVEKDCS QFGSNQELNS RFVYAKLRGA FSESTAVYPS AVGPKNQLIN PENKWKYWKV NVPDKPEHFV ELGAKDNPES KAIELSTLAL YGRNYDLDPT YKQKPVPINL SEQ ID NO: 40; Cluster ID (L) 64; Cluster ID (A) 16 Protein name: A0011; Species: Dermatophagoides pteronyssinus KSAPEGCFRA AVLDHVHQTD ARHLSNTAKI IDLNFKVYED AAALAKKQGA DIIVFPENGL IYSILSREKA DEFASDIPDA EVNACTLDSK FVYNRLACLA QKHQMFVVAD LIDRKSCEEL GINNVSDSCP ADKKFLFNTA VLFDRQGKLL GRYHKMHLFG EISMNPPPKP ELLVIDTELG RLGMQICFDM IFKTPGYLLA QENKFDTMLF PTWWFDESPM LSSSQYQMAW AFGNNVTLLA SNIHRIEVGS RGSGIYVGPH RTLAAALYDD SVERLVLANV PIKPKETDQS ACPLDSEIIE VPQQIPIPKS VKYHHQNLNL KDVTLLQLSS NESEVHLCHK GVCCQFEYRL AMKDQPQESW VDRVPLLANM LHYLTPEERY YLLIANRTRP GAYPWSEEFC AVVVCPSSRW NFGKMQKDCS KIGSNQELSS RFVHAKLRGK FSEDTAVYPS AVGSKNQLIY PENKWKFWKV NVPNEPEYFI ELGAKDNSES RAMELGALVL YGRNYNRDPR YEQKALPIN SEQ ID NO: 309 Protein name: A0011; Species: Blomia tropicalis GCFRAAVLDH VHQSSPNGGG TKENIKLNLK LYETAAKTAK EQGADIIVFP ENGIVYGIGS RANALKYGEI LPESKTSMCT DSYASSHPIA YQLACLAKEH QMFVAADMID VQTCQTKSCP IDKKYAFNTA VLFDRNGYLL GKYHKMHPFG ELQFNVPPKD ELVVIETEIG RLSMQVCFDL IYNKPGVVLA SQDKIDTMLF PTWWFDELPF LAASQYQMSW AFGNKINLLA SNIHLVAVGS KGSGIFAGGH GQFEVISEPD AKARILVATL PINARSDAQC SMDSKKIEVP QMVPIPSNVI YNYQMMNLTE NTVKKLDPSM EAISACDGGV CCQLNYQMDQ SSIKSDEEYY LIVTNRTRPG AYPWTEEYCG LVLCPHMTKL DTCKQISSNN PLQTKFLYAK LSGEFSSETH VYPSVIGSEH KVLPKDGGLW TYEDEKTDVG AKKQKFFITF GNKEERKSYT ISTIGLYGRV YARDPPYEQK PL SEQ ID NO: 22; Cluster ID (L) 103; Cluster ID (A) 19 Protein name: A0012; Species: Dermatophagoides pteronyssinus QSRDPNNKPY RIVCYWGTWA FYRPGTGKFE AENVNPNLCT HLMYGFAKLQ NNKIALYDPD LDDGDEDWNS GLNWGHGMIR RMVNLRTYNP HLTTMISIGG WNEGSDKYSM MVRDPSSRKI FIQSVLDLLA EFDLDGLDFD WEYPSMKATG DNDRKPGRDE DKEDFITLLR ELHEAFQPHG YLLSSAVSAG KPTIDRAYNI PEVSKYLDFI NLMSYDYHGG WESHTGHNAP LNSYDNANEL DKEFTVTYSV DYWLSHGVDA KN SEQ ID NO: 38; Cluster ID (L) 103; Cluster ID (A) 19 Protein name: A0012; Species: Dermatophagoides farinae QSRDPNDKPY RIVCYWGTWA FYRPASGKFQ AENVNPNLCT HIMYGFAKLQ NNKIALYDPD LDDGDEDWNS GLQWGHGMIR RMVNLRTYNP HLTTMISLGG WNEGSDKYSI MVRDPASRKI FIQSVLHLLA EFDLDGLDFD WEYPAMQASG DSDRKPGRAE DKEDFVTLLR ELHEAFQPHG YVLSSAVSAG KPTIDRAYNI PEVSKYLDFI NLMSYDYHGG WESHTGHNAP LNSYKNANEL DKEFTVTYSV EYWLNHGVDP KKLVLGIPLY GRTFTLAGSE HGIGAPTIGK GGESGTITRT IGMLGYNEIC TMIKQGWQLY RDEIERIPYA VHANQWIGYD DRESVNEKLN LLMAKHLGGA MVWSIDTDDF VGNCVGVKYP LLRSISKKLN NVDGPDPDIK RYHYHTSTAK PHTDGTTSTH HDHKTTTTKH HKTTQPHHKT TQPHHTQTIT TTTERPHGKF QCHQAGFFAD PENPRKFHQC VDFGGHLKDY EFMCGEGTHY DEKLHICVR SEQ ID NO: 310 Protein name: A0012; Species: Blomia tropicalis DRNKLPHKVV CYWGTWAFYR PGSDGKFEAE NINPNLCTHI NYGFAKLVGN KIALFDPDLD TGDEDWASGL TWGHGMIRRL NELRKYNKNL STLISIGGWN EGSNKYSTMV STAGGRSEFV KSVIEFLQKY EFDGLDLDWE YPGMSASGDA DRKPGREQDK ADYIELLKEL RQAFEPHGYI LSAAVSAGAP TIDRAYNVPE VSKHLHFINL MAYDFHGGWD TKTAHNAPLY ALPGAEGIDK EFTVSYAVEY WISKGADPKK LVLGIPLYGR TFTLAGPNHD IGAPVTGHGG QAGPITRLIG MLGYNEICSM VKNGWEIHWN DIQQIPYATH ASQWIGYDNE KSIEKKLDYV HQKNLGGGMV WSIDTDDFSG HCGVKYPLLK TISRRLNNID GPDVVIPRTH ATTPHPDDHD HTTKRPDDPH TDPHTEPHHD KTTSAPNPDG KFQCHSTGFF KDPSDPRKFH QCVDIGNGKL KDYEFNCPLG SHYDEQLHVC V SEQ ID NO: 36; Cluster ID (L) 40; Cluster ID (A) 23 Protein name: A0013; Species: Dermatophagoides farinae DTPANCTYED IKGLWLFEES TPINDRTEKC DNGRREYTKK IYVRLDFPNT AVDKFGNVGT WTLIYNQGFE VIINYRKYFA FSAYERKSNS KVISYCHKTI PGWSHDLLGN NWACYIGHKV NDWNSSPLQK IGSEQFPIKE HIEQPLYLKN IDLSHALSQN HVDQINSKQK SWKATVYPEM QSKTVEHLIK MAGGEKSRIM SRPKPIRATE QQRHEARGLP ESFDWRNVDG INYVSPVRNQ GNCGSCYAFA SMAMLEARIR IATNNTAKPV FSPQEVVDCS EYSQGCDGGF GYLIAGKYAQ DFGVVEESCY PYKAYTGKCK LDYNTTAKCQ QRTYTIKYNY LGGYFGACNE EAMRIELVKN GPIAVGFEVY KDFMTYRRGI YSHDSDYETE QKVGVEFNPF VLTNHAVLIV GYGRDEKSGE NYWIVKNSWG EQWGIDGGYF LIRRGTNECG IESIAMAATP IPN SEQ ID NO: 37; Cluster ID (L) 40; Cluster ID (A) 23 Protein name: A0013; Species: Dermatophagoides pteronyssinus DTPANCTYED IKGLWLFEET EPIKDRWEKC PEHQQQREKY SKKIFIRLDF PNVAVDKFGN IGEWTMIYNQ GFEVKINYRK YFAFSAYERK SENNVLSYCH KTQPGWSHDV LGNNWACYVG HKVNNWNDDD VSKTTTVGAE KFPVKQHSER ELYLQNINVE HILSQKHIDH LNSQQKSWKA IVYPDLQSKS IEHLIQMAGG RKSRIINRPK PLRATEQQKQ LARSLPESFD WRNLNGIDYV SPVRDQGKCG SCYTFASMAM LESRIRIQTN NTFKPIFSTQ EVVDCSEYSQ GCDGGFSYLI AGKYAQDFGV IDESCYPYKG VTGKCQNQQN FNQTNEKCKQ RTYTIDYKYV GGYFGACNEE AMQIELVQNG PIAVGFEVYG DFFGYSEGIY SHQPSNESND QHQQIKAEFN PFEMTNHAVL IVGYGKDKKT GEKYWIVKNS WGKQWGMDGY FWMRRGTDEC AIESLAMAAT PIPN SEQ ID NO: 311 Protein name: A0013; Species: Blomia tropicalis DTPANCTYED IRGEWEFHET ERIASRKEVC DDNSVSTTKH TVYLKLEFPN IATDQHGNVG HWTIIYNQGF EVSINYRKYF AFSLYKQVGK QVTSYCDSTF PGWSHDVLGN NWACFKGRKV NRQQEKSFDE TMINNGKTHT VQPFLLESVP VNHNLIQMNV NKINMKQSSW KAKFYPHLMN LNTEDLIRMA GGRGSAIVNR PSTVPASEEI KEKVRQLPES FDWRNVNGIN YVSPVRDQGK CGSCYIFSSM AQLEARVRIA TNNSEQPIFS TQEVVDCSKY SQGCDGGFPY LIAGKYGRDY GVIADECYPY KGKNGKCSLP YNSTGTKCMK RSYTLHYHYV GGYYGGCNEE LMLLELVKNG PITVGFEVYD DFTSYSGGIY SHDKSKDQWR NGVHFNPFQL TNHAVLIVGY GVDKQSGEKY WIVKNSWGKD WGLDGYFWIK RGNDECGIES LAVSVTPIP SEQ ID NO: 32; Cluster ID (L) 33; Cluster ID (A) 25 Protein name: A0014; Species: Dermatophagoides farinae IEQVHISLGT NATEMIVTWT EPQKHTDIDI DAVVYYGRAS SSFDQAAIAK SEHFKDDETK YTTFRALLTG LESDTRYHYK IQLDDKESSI FAFKTLKLDE NWLPRFAIYG DLGYVNEQSL PYLKKDVEKN MFDVIFHIGD IAYDLQDENG EVGNNFMRSI ESIASKIPYM TCPGNHERHS NFSHYDSRFS MIGDRSQPNH QDSLDKRINN HFHSMEIGPA TIIMFSTEYY YYTYYGWEQI ERQYRFLEKE LIRANENRNK RPWIIAMGHR PLYCLKMGDS SCDHQTMERP EIRQGIRMHD QGERQYGLED LFHKYGVDIQ FYGHEHFYAR MFPIYKYQMY KGKQSDNPYD HADGPIHITT GSAGNKEIHP LFNHLKEWVA HHFYDYGYTR LIFENQYRIR LQQVSDDQHG KVLDEIEIIK SSPQPHWMP SEQ ID NO: 33; Cluster ID (L) 33; Cluster ID (A) 25 Protein name: A0014; Species: Dermatophagoides pteronyssinus IEQVHIALGS NETEIIVTWT EPHKHDDKTS DAVVYYGQAK SSFDQKVKAI SEYFKDDKTK YTTYRALLTG LLPGTEYHYR IQMDDLESSI FEFKTLKTGE ENWLPRFAIY GDLGYVNEQS LPYLKKDVEQ NLFDVIFHIG DFAYDLNDEH GKVGHHFMRS IEPVASKVAY MTCPGNHERH DNFSHYDSRF SMIGDRSQPI HSDKLNKRLN NHFHSMTIGP ATIILFSTEY YYYTKYGWQQ IEHQYRWLEQ ELKRANENRQ KHPWIIVMGH RPLYCLKMGD DSCDHQTMER KEIRQGIRMH DEGERQYGLE DLFFKYGVDI QFYGHEHFYA RLFPIYKYKM YNGTKSKNPY DHPGAPIHIT TGSAGNKELH PEFNHLNDWV AEHFYDYGYT RLMFEDKYRI RLQQISDDQH GKVLDEIEIV KSSPQPHWMN VEHH SEQ ID NO: 26; Cluster ID (L) 25; Cluster ID (A) 34 Protein name: A0015; Species: Dermatophagoides farinae SPTSIRTFEE FKRQFNKQYQ SIEHEEIARK NFQETLRYVQ ANQDKAVINE YADLSAEEFA DGYLMNVQDV QDLEAEMDAE KEYFDDPDCK LHGDFNPPKE FDLRPHLTPI KKQIKNCGCC WALSTISCVE TAYLAQKNVS LQLSTQELVN CAKEHGCKKG TVLDGIEYIM ANGTTTEEAC PFISEESTCD QSKKPRYEIS NWCYFKPVED DIRKNLVLRR TSVSVSMNIE NLKAFVHYDG SFVIRENSFP SIGNKSYHAV NIVGFGTKDD IDHWIVRNSW GEKWGDKGYF YVERDINLWG IKDWAFTTIV SEQ ID NO: 27; Cluster ID (L) 25; Cluster ID (A) 34 Protein name: A0015; Species: Dermatophagoides pteronyssinus SPTGWNIRTF EQFKIQFNKH YDSIEQEEHA RENFLETLKY VDANPDKAVI NEFADLSAEE FADGYLMSEE SMQDSEQQLK LLRAGYDYHD DPECLFDENL EAPKQVDLRP DLSPIMRQTL HCGCCWAISP ISSAESAYKA RYNVSIQLSV QELVNCAVEH GCEIGKTAIA FNYLVTNGTT TQKAYPYTAK EGACNPPEKP

RYTLENWCAY IDPSIKNKNK PDLRKVLAQK RTSITVQISI KNVKAFAHHN GSFIIRENSF PDEGKPSGHA INIVGYGTKD GVDYWIVRNS WSTGWGDKGY FYVERGVNWW GIEEYAFIAT F SEQ ID NO: 312 Protein name: A0015; Species: Blomia tropicalis IKTFEQFKKV FGKVYRNAEE EARREHHFKE QLKWVEEHNG IDGVEYAINE YSDMSEQEFS FHLSGGGLNF TYMKMEAAKE PLINTYGSLP QNFDWRQKAR LTRIRQQGAC GSCWAFAAAG VAESLYSIQK QQSIELSEQE LVDCTYNRYD SSYQCNGCGS GYSTEAFKYM IRTGLVEERN YPYNMRTQWC DPDVEGQRYH VSGYQQLRYQ SSDEDVMYTI QQHGPVVIYM HGSNNYFRNL GNGVLRGVAY NDAYTDHAVI LVGWGTVQGV DYWIIRNSWG TGWGNGGYGY VERGHNSLGI NNFVTYATL SEQ ID NO: 28; Cluster ID (L) 43; Cluster ID (A) 39 Protein name: A0016; Species: Dermatophagoides farinae MVKIGINGFG RIGRLVLRAA VKKGVEVVAV NDPFLDVKYM VYMFKFDSTH GRYQGEVKEE GGLLVVDGQK IQVFQERNPA DIPWGKVGAD YVVESTGVFT TIEKAKAHLA GGAKKVVISA PSADAPMYVM GVNHDKYDPS QQIISNASCT TNCLAPLAKV INDKFGIENG LMTTVHAVTA TQKTVDGPSG KMWRDGRGAG QNIIPASTGA AKAVGKVIPE LNGKLTGMAL RVPVPDVSVV DLTVTLKNPA SYDEIKAAIK AAAESDHWKG ILEYTDEEVV SSDFISDTHS SIFDAKAGIA LTPTFVKLIA WYDNEFGYSN RVIDLIKYVA SK SEQ ID NO: 29; Cluster ID (L) 43; Cluster ID (A) 39 Protein name: A0016; Species: Dermatophagoides pteronyssinus MVKIGINGFG RIGRLVLRAA IKKGVEVAAI NDPFLDVKYM VYMFKFDSTH GRYQGEVKEE GGLLVVDGQK IQVFQERNPA EIPWGKVGAD YVVESTGVFT TIEKAKAHLA GGAKKVIISA PSADAPMYVM GVNHDKYDPK QQIISNASCT TNCLAPLAKV INDKFGIENG LMTTVHAITA TQKTVDGPSG KLWRDGRGAG QNIIPASTGA AKAVGKVIPE LNGKLTGMAL RVPVPDVSVV DLTVTLKNPA SYDEIKAAVK AAAESDHWKG ILEYTDEEVV SSDFISDTHS SIFDAKAGIA LTPTFVKLIA WYDNEFGYSN RVVDLIKYVA SK SEQ ID NO: 21; Cluster ID (L) 13; Cluster ID (A) 49 Protein name: A0017; Species: Dermatophagoides farinae MSSSSGKKYD FSGKVALVTG SSSGIGAAIA VQFAQYGAKL TITGRDGAAL ESVAKKIEIE SGHQPLQIVG DLLDQSLPAK LINETVSKFG RLDFLVNNAG GSTAHRELND EKLMEAFDKV FALNVRAVLQ LSQLAAIHLE KSKGNIINIS SIVSMKPYGH VYSSSKAALD MITKTLAKEL GLKGVRVNSI NPGPVATGFL RSVGMSATAY TDLADTMINH TLLKFLAQPD EIANLASFLA SDDARNMTGS IVVSDTGSLL V SEQ ID NO: 25; Cluster ID (L) 13; Cluster ID (A) 49 Protein name: A0017; Species: Dermatophagoides pteronyssinus MSSSSGKKYD FSGKVALVTG SSSGIGAAIA LQFAQYGAQV TITGRDAAAL ESVAKRIEAE SGHQPLQIVG NLLDQSLPAK LIDGTISKYG RLDFLVNNAG FSTQHRDIHD EKLMEAFDQV YGLNVRAVVQ LSQLAATHLE KSKGNIINIS SNLSMMPVHI IYSSSKAALD MITKTMAMEF GKKGVRVNSI NPGPVATQFM RSLGMPVTFL KENEEFVKEL TLLKFVAQPV EIANLASFLA SDDARNMTGS IVVNDTGSLL APRVDFKKLD EIKKK SEQ ID NO: 313 Protein name: A0017; Species: Blomia tropicalis SLTNKKYDFS GKVALVTGSS SGIGAAIAIQ FAQYGAKVTI TGRNAENLDK IAKKIAEVSN GVEALQIIGD LTIDDSLPKR LIDETVTKFG RLDFLVNNAG GATPQGTLAS PDLLKGFDDV FKLNVRSVIE LTQLAMPHLE KTKGNIINIS SVASIKPYMV VYSSSKAALD MITKTSALEL GPKGIRVNSI NPGPVVTAFG RSMGVDPSHH KKMFDSFEKQ MLMERVGQPE DIANLASFLA SDDAINITGS IMVNDSGCLL SEQ ID NO: 5; Cluster ID (L) 97; Cluster ID (A) 71 Protein name: A0018; Species: Dermatophagoides farinae MVKAVVVLKG EPNVTGTIFF EQQDNGPVKV SGTVQGLKSG LHGFHVHEFG DNTNGCTSAG AHYNPFNKTH GAPADEERHV GDLGNVEAND AGIANVAIED SLISLTGERS IVGRSLVVHA DPDDLGRGGH ELSKTTGNAG GRLACGVIGV TK SEQ ID NO: 6; Cluster ID (L) 97; Cluster ID (A) 71 Protein name: A0018; Species: Dermatophagoides pteronyssinus MVKAVVVLKG DPNVSGTIFF EQQDNGPVKV TGSVQGLKPG LHGFHVHEFG DNTNGCTSAG AHYNPLNKTH GAPNDEERHV GDLGNIEAND KGVANVVIED SLISLTGEKS IVGRSLVVHA DPDDLGRGGH ELSKTTGNAG GRLVCGVIGV TK SEQ ID NO: 314 Protein name: A0018; Species: Blomia tropicalis KAVVVLKGDS PVSGTIFFEQ KDNGPVSVTG TVNGLTAGDH GFHVHEFGDN TNGCTSAGAH FNPFGKTHGA PADQERHVGD LGNVTADANG VANVNIQDSL ITLEGANTIV GRSLVVHADP DDLGRGGHEL SKTTGNAGGR VACGVIGLTK SEQ ID NO: 1; Cluster ID (L) 75; Cluster ID (A) 75 Protein name: A0019; Species: Dermatophagoides farinae DGSHIVKAAR SQIGVPYSWG GGGIHGKSKG IGEGANIVGF DCSGLAQYSI YQGTHKTIAR TAAAQYNDNH CHHVAYGSHQ PGDLVFFGNP IYHVGIVSAH GRMVNAPKPG TKVREENIWS YHISHVARCW SEQ ID NO: 4; Cluster ID (L) 75; Cluster ID (A) 75 Protein name: A0019; Species: Dermatophagoides pteronyssinus QVYCNGAAIV SAARSQIGVP YSWGGGGIHG KSRGIGEGAN TVGFDCSGLA QYSVYQGTHK VLARVASGQY SDPKCHHVAY GSHQPGDLVF FGNPIHHVGI VSAHGRMINA PHTGTNVREE NIWSDHIANV ARCW SEQ ID NO: 315 Protein name: A0019; Species: Blomia tropicalis QAMAGGHEIV TAARSQLGVP YSWGGGNWAG KSKGIDSGAH TVGFDCSGLA QYAVYHGTHK KIARVASAQY ADHQCHHVPY AQHLPGDLVF FNDGGSIHHV AIISGKNTMI HAPHTGDHVR EAAVYVKGRM STVQRCF SEQ ID NO: 15; Cluster ID (L) 31; Cluster ID (A) 59 Protein name: A0020; Species: Dermatophagoides farinae MSKPTFYFHP FSGPCRTVST VAKILNVEME MKKLDLLTQE HLKPEFLKVN PFHKIPTFVD TDGFTIDESR VIAMYLLQSR KPDSFLYPNN DLKKRTQIDR WLHYDISFAT IISTPMYCKF RGKPVQDHQV EQGKETLKTL DGVMASFGGK FLTGSDQITL ADIAMYFSCN TMEIYSEYFK FDDYPNLKSW YQRVAEALKQ YDTEGEIPKA IEMIKQFAQQ RMAESAKQ SEQ ID NO: 16; Cluster ID (L) 31; Cluster ID (A) 59 Protein name: A0020; Species: Dermatophagoides pteronyssinus MSKPIFYYHP FSGPCRTVST VAKILNVDME MKKLDLLTKE HLNPEFLKVN PFHKVPTFVD SDGFVVDESR VIAMYLVESR KPDSFLYPKN DLKKRIQIDR WLHYDINLST TISAPMFCVF RGHQVQDYQV EQGKETLKTL DGVMQSFEGK FLTGADQFTL ADIAMYFSLN TMEVYPKYFK FDDYPNLKSW YHRVAEALKQ YDTEGTIPKA IETMKQFIQQ RAAEAEKH SEQ ID NO: 316 Protein name: A0019; Species: Blomia tropicalis MSKPTLYYMW ESPPCCTVIA IARILNIELD MKHVDLTKKD QNNPEFKKIN PFAIVPTFVE TDGYTLWESR AISTYLVQSR SPDSTLYPGS DLKKRSTIDK FLQYDLGTFN RAIYDVVSEI FKSGKLNEQN IPRLGEVLKT LEETLAANNE SNGGPFITGD DQLTIADISM HFSWTLLSLL PERLIDQSSY PTIRAWNQAV IQALKPYNRD QKFTEAQRRL KAFITMMIES AKN SEQ ID NO: 19; Cluster ID (L) 105; Cluster ID (A) 50 Protein name: A0022; Species: Dermatophagoides farinae EWRLVWQDEF NGNQLDLNQW SYEVGGNGWG NNELEFYTYN RTENARIENG NLVIDVRVEN YRERQFTSAR LHTRQAWTYG RFEARARMPY GHNLWPAIWM MPQDSIYGIW AASGEIDIVE YRGDNPDRIE GTAHYGGTWP NHIYSGSGPR SFSVNFSQDF HTFALEWDHK QLRWYMDNQQ YFTLDIDRML WSGKGVNPYT KNGQPFDQPF HWMLNVAVGG NFFGPGPYVT PDQARQWPKH TLEIDYVRVY QQ SEQ ID NO: 20; Cluster ID (L) 105; Cluster ID (A) 50 Protein name: A0022; Species: Dermatophagoides pteronyssinus NWQMVWQDEF NGGHLDQNHW EFETGGGGWG NNELEFYTAN RSQNVRVENG HLVIDVRVES YGGRDFTSGR IHSKQAWAYG KFEARARLPS GHHLWPAIWM FPRDSKYGPW AASGEIDIME YRGDVHDKIE GTIHYGGQWP NNIYTGSGPH HFNVDFSKDF HNFAVEWDTK EIRWYMDGNK YFSVNIDRNM WSGKGNNPYN KNGQPFDQPF RWILNVAVGG NFFGPGPYVT PDQARHWQKH TMEIDYVRVY QWR SEQ ID NO: 317 Protein name: A0022; Species: Blomia tropicalis NWQLVWSDEF NGNGLDENNW NYQTGCSQQN DELECYTSHR HENVRVENGH LVIEARPEEY QGHHFTSGRL HGKKAWAYGK FEARAKMPSG HHLWPAIWMM PRDSKYGGWA ASGEIDILEL RGDKPHEIVG TIHYGGSWPN NIYHGSGERY YQQDFSQDYH TFAVEWDQKE IRWYVDGQHY HTENIDRNMW SGRGNNPYHK NGEPFDQPFY WILNVAVGGN FFGPGPYVSP AEARNWHKRT MEVDYVRVYQ WR SEQ ID NO: 23; Cluster ID (L) 8; Cluster ID (A) 42 Protein name: A0023; Species: Dermatophagoides farinae SPAQRPSLRG VTIRNAPFLE EIDGKFKGFI PDLMDAIAEK AGFDYTLYLS PDGRYGNADK EGNVTGMIGE VYNKKADFAA ADLTMTEARE NYITFTEPFM INQLAALIRR EDAEGMNTLE DLVNAGKTQP NHKPIILGTL RNGATNHFLS KSDDPLAKKM YEQIKANDQS ATTSISKGIE RVDKQGGYAF IMESSSAEHE IANNCKLTML LDWRNLYPRK YAFALPKDSQ YLQHFNNAIK QLNTEDKIAE LRRKYWSNNC SNTQTKNTGA SEQ ID NO: 24; Cluster ID (L) 8; Cluster ID (A) 42 Protein name: A0023; Species: Dermatophagoides pteronyssinus DPVQQRPTLR GVTVRVGPFV KENNGKFEGF IPDLVQAISE KVGFDYTLYL SPDGRYGNVI SDGNVTGMIG EVYNKKADFA AADLTMTEAR ENYITFTEPF MINQLAALIR REDAEGLNTL EDLAKAQETF PKRKRIVLGT LRNGATNYFL SKSDDPLAKK IYEQIKADDQ SVVKSISEGV ERVDKQGGYA FIMESASAEH EIANNCKLTM LLDWPNLFPR KYAFALPKDS PYLEHFNNAI KQLNSEGKIA ELRRKYWANN CAENKTKDDK N SEQ ID NO: 11; Cluster ID (L) 36; Cluster ID (A) 65 Protein name: A0024; Species: Dermatophagoides farinae MSISAEGGGL VNGIAGMENK FTVFTSGKPV SGLTVAFEGP TKPEINFNST KDGSVDVGYT PKAGGQYKIH IKYEGKEIVG SPFKCNISGD EATHRKLTEK VKVGGPNINA GKVNQDNQLT IDCKEAGITG GISFAMEGPA KVEVSFRNNN DGTITVIYKP PTPGDYKLHL KFNDIHLPGS PYPIVVAA SEQ ID NO: 12; Cluster ID (L) 36; Cluster ID (A) 65 Protein name: A0024; Species: Dermatophagoides pteronyssinus MSISAEGGGL VNGIAGMENK FTVFTSGKPV SGLTVAFEGP TKPEINFNST KDGSVDVGYI PKAGGQYKIH IKYEGKEIVG SPFKCNISGD ESTHRKLTEK VKVGGPNIST GKVNQDNQLT IDCKEAGITG GISFAMEGPA KVEVSFRNNN DGTITVIYKP PTPGDYKLHL KFNDIHLPGS PYPIVVSA SEQ ID NO: 318 Protein name: A0024; Species: Blomia tropicalis MSISAEGGGL INGIAGMENK FTVFTSGKPV SGLTVAFEGP TKPDINFNSA KDGSVDVSYT PKAGGMYKIH IKYDGKEIIG SPFKTNITGD EATHRKLTEK VKVGGPNVST GKANADNELT IDCKEAGITG GISFAMEGPA KVEVSFRNNN DGTITVVYKP PQNGDYKLHL KFNDIHLPGS PFPIVVS SEQ ID NO: 17; Cluster ID (L) 104; Cluster ID (A) NA Protein name: A0025; Species: Dermatophagoides farinae ESLFIYDDYS CGSYGHDVNE LIEQFQLFKK NEHNQNESIE IIGHFLKKIR EYRVEAIKVM LETDRKLLTL NNSQIILNIQ YQKKKIRCEN LKHLSELLTM HLLAYKQGMF DFAEEIDPDV NFDRQFKNFL DRSSEVMNIN EFSDIEKKWS NSSAKKLLKN DIDGLITALD DLREDFLKNI ILPEFDAQSR YDLYFSIQDQ INIRSTLKLF GTIKMFMKEL LDDLNQPDFE ILY SEQ ID NO: 18; Cluster ID (L) 104; Cluster ID (A) NA Protein name: A0025; Species: Dermatophagoides pteronyssinus QSLFVDYNDY SCGSSQNETN ELIQEFKIFK KNINGNENFK KINDFIEKAR LFRDNAAKQM LEIDQQLLTL NVIQISQRIK LENNKIQCEK LTKFSELLSM QLLAYEVGMF EFAEEIDPNI DFDRKMKNFL DETSRLFNLA EFEKLEKKFR NATSIEKLKN YIDGELVALN DYINEFLKDI IMSEFTVQSR YYLNFSIEDQ VQIDSTLMTF SALKILLNDL KDYLEHLDN SEQ ID NO: 9; Cluster ID (L) 102; Cluster ID (A) 62 Protein name: NA; Species: Dermatophagoides farinae NRVSVGVYYE TICSGCRTHF INAIVPLRQQ LGEYVDIDLV PFGNAEIYSN GPQCQHGALE CYGNAFQACS LDMNGFDTGF KLVECMFRSS YYSNPQYSAK RCAQQLNLNY DQLHSCATGQ KGFELIKVMA RKTPRHNYVP WTTVESRTVD VNVDLVKYIC DNYLNNVPAC N SEQ ID NO: 10; Cluster ID (L) 102; Cluster ID (A) 62 Protein name: NA; Species: Dermatophagoides pteronyssinus TQRVTVGVYY ETICPGCRSH FIQAIVPLKN QLGQYVNIDL VPFGNAHFYS NGPQCQHGQL ECYGNAFQAC SLDMNGFETA FKLVECMFRS NYFSNPEYSS KQCSQQLNLD YQQLDSCANG QKGLQLIREM ANKTPSHQYV

PWTTVQGRFV DGNVDLVDYI CENYLNGVPA CN Each of the above amino acid sequences (SEQ ID NOs: 1-44 and 305-318) can according to the present invention be modified by substituting each cysteine residue with at least either a serine residue, an alanine residue or a 2-aminobutyric acid (also known as a-butyric acid and homoalanine) residue. The sequences of the thus modified variants of SEQ ID NOs: 1-44 and 305-318 are set forth in SEQ ID NOs: 261-304 and 319-332.

[0320] In embodiments of SEQ ID NOs: 261-304 and 319-332, all cysteine residues in an amino acid sequence are substituted with serine residues. In other embodiments of SEQ ID NOs: 261-304 and 319-332, all cysteine residues in an amino acid sequence are substituted with an alanine residue. In other embodiments of SEQ ID NOs: 261-304 and 319-332, all cysteine residues in an amino acid sequence are substituted with 2-aminobutyric acid residues. Further, in a group of embodiments of SEQ ID NOs: 261-304 and 319-332, more than 1 of serine, alanine and 2-aminobutyric acid substitutions can be present in the same amino acid sequence and in some embodiments all 3 substitutions are present in the same amino acid sequence..

[0321] SEQ ID NOs: 45-260 refer to 15-mer peptides of the invention that are fragments of proteins of SEQ ID NOs: 1-44:

TABLE-US-00002 SEQ ID Source Peptide Start NO: Protein ID Species ID # pos Sequence 45 A0001 Der f/p 2344 131 IMRILCCKSRKVAPC 46 A0007 Der f/p 1800 4 FNYLPVDVQEELRNT 47 A0007 Der f/p 1805 94 ELLKKKGIIPGIKVD 48 A0007 Der f/p 1804 69 EQYISGVILFDETVY 49 A0007 Der f/p 1806 99 KGIIPGIKVDTGVVT 50 A0008 Der f/p 1360 9 FIMLKPDAVQRGIVG 51 A0008 Der f/p 1361 19 RGIVGEIIRRFEAKG 52 A0008 Der f/p 1362 24 EIIRRFEAKGFKLVA 53 A0008 Der f/p 1363 29 FEAKGFKLVAMKFMM 54 A0008 Der f/p 1364 34 FKLVAMKFMMASEDL 55 A0008 Der f/p 1365 40 KFMMASEDLLKKHYA 56 A0008 Der f/p 1366 49 LKKHYADLAARPFFP 57 A0008 Der f/p 1368 79 WEGLNAVKTGRVMLG 58 A0009 Der f 1710 387 ITRLREAMGVMQHHD 59 A0009 Der f/p 1711 405 GTEKQHVAFNYAKML 60 A0009 Der f/p 1712 410 HVAFNYAKMLDSAML 61 A0009 Der f 1714 422 AMLQCRHVISESYRK 62 A0009 Der p 1715 427 RHIINESYKKLLPKS 63 A0009 Der f 1716 447 EFCPYLNISSCPSTE 64 A0009 Der p 1718 470 LYNPLGHRLINHTVR 65 A0009 Der f 1722 507 LISIPEFVRKIPGRK 66 A0009 Der f 1742 647 IVQEVHQQFDSFVGQ 67 A0009 Der f 1757 778 LMVHRRLLHDDYFGV 68 A0009 Der f 1758 802 DGHGIVIRGRHLLLL 69 A0009 Der p 1767 842 EPIISFTSIESNKQA 70 A0009 Der f 1776 872 HSKRYLLRLEHFYQR 71 A0009 Der f 1777 878 LLRLEHFYQRFEDPS 72 A0009 Der p 1778 885 KRYLLRLEHFYQSNE 73 A0009 Der f 1775 888 TLEQWHSKRYLLRLE 74 A0009 Der f 1779 897 TVSLRHLFQSFEITA 75 A0009 Der p 1782 910 SLRHLFKSFEIIAVE 76 A0009 Der p 1783 915 FKSFEIIAVEELTLG 77 A0009 Der p 1786 930 ANQPISSLKNRLHYR 78 A0009 Der p 1785 990 ELTLGANQPISSLKN 79 A0010 Der f 305 38 GNDLKNLSSKVLPNL 80 A0010 Der f 307 43 NLSSKVLPNLNVPYC 81 A0010 Der p 306 44 DDGNLISRALPHLGV 82 A0010 Der f 309 63 YIGYKIEKHSKNLIQ 83 A0010 Der p 312 81 DLSMTKLKRVRPSGF 84 A0010 Der p 313 106 IHQLNDQVLRLKFID 85 A0010 Der p 314 111 DQVLRLKFIDANQKR 86 A0010 Der f 315 138 RLYSVELDGSHLIVR 87 A0010 Der f 316 158 QSIFDINLAYMVYSD 88 A0010 Der f 318 168 MVYSDQLIHVTSRLP 89 A0010 Der f 321 193 RAPFRKNTNWKRYTQ 90 A0010 Der p 324 241 TKLASGVFLFNSNAM 91 A0010 Der p 325 246 GVFLFNSNAMDILTQ 92 A0010 Der p 330 281 GPKPEQVVQQYHNLI 93 A0010 Der p 331 286 QVVQQYHNLIGLPAM 94 A0010 Der f 334 313 FTNLNTTYTRNRAVG 95 A0010 Der f 335 348 TTYTRNRAVGIPMDV 96 A0010 Der p 337 361 LPDFIRNVLHKNGQK 97 A0010 Der f 340 428 NATEYWMDMFAEYHK 98 A0010 Der f 341 433 WMDMFAEYHKTIAFD 99 A0010 Der f 342 438 AEYHKTIAFDGAWLD 100 A0010 Der f/p 343 487 TLRHKTLCMTARHYN 101 A0010 Der f/p 344 498 RHYNDQLHYNLHNLY 102 A0010 Der f 346 508 QLHYNLHNLYGFQEA 103 A0010 Der f 345 508 QLHYNLHNLYSLSMA 104 A0010 Der f 347 508 LHNLYSLSMAMATNA 105 A0010 Der f 348 513 SLSMAMATNAALTKL 106 A0010 Der f 350 522 AALTKLNKRPFIISR 107 A0010 Der p 349 526 NEALKTTLNKRPFII 108 A0010 Der f 351 528 NKRPFIISRATAPGH 109 A0010 Der f 352 548 HWNGDILSDWSSMRW 110 A0010 Der f 353 553 ILSDWSSMRWTIPSI 111 A0010 Der f 354 558 SSMRWTIPSILNFNM 112 A0010 Der p 355 571 PSILNFNLFGVPMIG 113 A0010 Der f 356 593 LCIRWYQLGAFYSFA 114 A0010 Der f 357 598 YQLGAFYSFARNHND 115 A0010 Der p 358 608 AFYSFVRNHNTDNAI 116 A0010 Der f 359 623 LGESVIRAARSSLQY 117 A0010 Der f 360 628 IRAARSSLQYRYRFL 118 A0010 Der f 361 633 sSLQYRYRFLAHLYT 119 A0010 Der f 362 638 RYRFLAHLYTLFYHV 120 A0010 Der f 363 643 AHLYTLFYHVHKNGG 121 A0010 Der p 364 681 DIETQFMWGDSMLIA 122 A0010 Der p 365 686 FMWGDSMLIAPILYP 123 A0010 Der f 366 728 YDDIDYVFVRGGSII 124 A0010 Der p 367 736 DINYVFFRSGSIIPI 125 A0010 Der p 368 741 FFRSGSIIPIQGPQN 126 A0010 Der f 375 816 TQNINFINILGVPKL 127 A0010 Der p 373 816 SQHLGYQTNQSIIIL 128 A0010 Der p 374 821 YQTNQSIIILEILGI 129 A0010 Der f 377 822 INILGVPKLPTSFKL 130 A0010 Der p 378 841 SIIFDGKPYYQFIYT 131 A0010 Der f 380 843 PRIIRFNYDEQTNIL 132 A0010 Der p 379 846 GKPYYQFIYTTNNML 133 A0010 Der p 381 851 QFIYTTNNMLIIQTK 134 A0010 Der p 382 856 TNNMLIIQTKLSIFN 135 A0010 Der p 383 861 IIQTKLSIFNDNDKS 136 A0010 Der p 384 873 DKSKKIHYQFEWKFN 137 A0010 Der f 369 885 HDNTELMKTKDFLLI 138 A0010 Der p 332 887 YHNLIGLPAMPPFWS 139 A0011 Der f 1859 32 ELNFKVYEDAAALAK 140 A0011 Der f 1860 57 EDGLIYNIASREKAD 141 A0011 Der f 1861 102 KHEIFVVADLIDRKS 142 A0011 Der f/p 1862 132 DKKFLFNTAVLFDRQ 143 A0011 Der f/p 1863 137 FNTAVLFDRQGKLLG 144 A0011 Der f 1865 152 RYHKMHLFGEMTMNI 145 A0011 Der f/p 1866 167 PPKPELLVIDTELGR 146 A0011 Der f/p 1867 172 LLVIDTELGRLGMQI 147 A0011 Der f 1868 185 LGMQICFDMIFKTPG 148 A0011 Der f 1870 212 TWWFDEAPMLSSSQY 149 A0011 Der f/p 1871 222 ssSQYQMAWAFGNNV 150 A0011 Der f 1880 427 ELNSRFVYAKLRGAF 151 A0011 Der f 1881 432 FVYAKLRGAFSESTA 152 A0011 Der f 1882 437 LRGAFSESTAVYPSA 153 A0012 Der f 2421 17 GTWAFYRPASGKFQA 154 A0012 Der f 2422 37 NLCTHIMYGFAKLQN 155 A0012 Der f 2423 42 IMYGFAKLQNNKIAL 156 A0012 Der f 2424 72 LQWGHGMIRRMVNLR 157 A0012 Der f/p 2425 74 GMIRRMVNLRTYNPH 158 A0012 Der f/p 2426 82 MVNLRTYNPHLTTMI 159 A0012 Der f 2428 107 KYSIMVRDPASRKIF 160 A0012 Der f 2429 117 SRKIFIQSVLHLLAE 161 A0012 Der f 2430 122 IQSVLHLLAEFDLDG 162 A0012 Der f 2431 161 KEDFVTLLRELHEAF 163 A0012 Der f 2432 177 QPHGYVLSSAVSAGK 164 A0012 Der f/p 2433 202 EVSKYLDFINLMSYD 165 A0012 Der f/p 2434 207 LDFINLMSYDYHGGW 166 A0012 Der f 2435 242 KEFTVTYSVEYWLNH 167 A0012 Der f 2436 257 GVDPKKLVLGIPLYG

168 A0012 Der f 2437 269 LYGRTFTLAGSEHGI 169 A0012 Der f 2441 347 EKLNLLMAKHLGGAM 170 A0012 Der f 2442 372 GNCVGVKYPLLRSIS 171 A0012 Der f 2443 377 VKYPLLRSISKKLNN 172 A0012 Der f 2445 457 HGKFQCHQAGFFADP 173 A0013 Der f 1096 13 GLWLFEESTPINDRT 174 A0013 Der f 1097 38 TKKIYVRLDFPNTAV 175 A0013 Der f 1099 63 LIYNQGFEVIINYRK 176 A0013 Der f 1100 68 GFEVIINYRKYFAFS 177 A0013 Der f/p 1101 73 INYRKYFAFSAYERK 178 A0013 Der f 1102 78 YFAFSAYERKSNSKV 179 A0013 Der f 1113 253 AMLEARIRIATNNTA 180 A0013 Der f 1115 287 DGGFGYLIAGKYAQD 181 A0013 Der f 1116 333 TYTIKYNYLGGYFGA 182 A0013 Der f 1117 353 MRIELVKNGPIAVGF 183 A0013 Der f 1118 363 IAVGFEVYKDFMTYR 184 A0013 Der f 1119 368 EVYKDFMTYRRGIYS 185 A0014 Der p 1006 31 DAVVYYGQAKSSFDQ 186 A0014 Der f/p 1009 110 GDLGYVNEQSLPYLK 187 A0014 Der p 1012 155 HFMRSIEPVASKVAY 188 A0014 Der p 1013 186 YDSRFSMIGDRSQPI 189 A0014 Der p 1014 211 NHFHSMTIGPATIIL 190 A0014 Der p 1015 221 ATIILFSTEYYYYTK 191 A0014 Der p 1016 261 KHPWIIVMGHRPLYC 192 A0014 Der p 1017 306 QYGLEDLFFKYGVDI 193 A0014 Der p 1018 311 DLFFKYGVDIQFYGH 194 A0014 Der p 1019 326 EHFYARLFPIYKYKM 195 A0014 Der p 1020 331 RLFPIYKYKMYNGTK 196 A0014 Der p 1021 336 YKYKMYNGTKSKNPY 197 A0014 Der p 1022 371 PEFNHLNDWVAEHFY 198 A0014 Der p 1023 381 AEHFYDYGYTRLMFE 199 A0014 Der p 1024 386 DYGYTRLMFEDKYRI 200 A0014 Der p 1025 391 RLMFEDKYRIRLQQI 201 A0016 Der f/p 1353 3 KIGINGFGRIGRLVL 202 A0017 Der f/p 404 9 YDFSGKVALVTGSSS 203 A0017 Der f 406 29 IAVQFAQYGAKLTIT 204 A0017 Der f 407 69 VGDLLDQSLPAKLIN 205 A0017 Der f 412 124 NVRAVLQLSQLAAIH 206 A0017 Der f 413 129 LQLSQLAAIHLEKSK 207 A0017 Der f 421 179 ELGLKGVRVNSINPG 208 A0017 Der f 425 219 NHTLLKFLAQPDEIA 209 A0017 Der f 428 247 MTGSIVVSDIGSLLV 210 A0018 Der f 2351 3 KAVVVLKGEPNVTGT 211 A0018 Der p 2352 93 VANVVIEDSLISLTG 212 A0018 Der f 2353 98 IEDSLISLTGERSIV 213 A0018 Der f 2354 103 ISLTGERSIVGRSLV 214 A0018 Der p 2355 108 EKSIVGRSLVVHADP 215 A0019 Der p 2065 3 YCNGAAIVSAARSQI 216 A0019 Der p 2066 8 AIVSAARSQIGVPYS 217 A0019 Der p 2067 53 SVYQGTHKVLARVAS 218 A0019 Der p 2068 86 GDLVFFGNPIHHVGI 219 A0019 Der p 2069 93 NPIHHVGIVSAHGRM 220 A0019 Der p 2070 98 VGIVSAHGRMINAPH 221 A0020 Der f 968 42 LKPEFLKVNPFHKIP 222 A0020 Der f 969 47 LKVNPFHKIPTFVDT 223 A0020 Der f 970 52 FHKIPTFVDTDGFTI 224 A0020 Der f 971 62 DGFTIDESRVIAMYL 225 A0020 Der f 978 157 QITLADIAMYFSCNT 226 A0020 Der f 979 162 DIAMYFSCNTMEIYS 227 A0022 Der p 2481 168 DTKEIRWYMDGNKYF 228 A0022 Der p 2485 238 QKHTMEIDYVRVYQW 229 A0023 Der f 178 7 SLRGVTIRNAPFLEE 230 A0023 Der f/p 179 87 EARENYITFTEPFMI 231 A0023 Der f/p 180 92 YITFTEPFMINQLAA 232 A0023 Der f/p 181 97 EPFMINQLAALIRRE 233 A0023 Der f 182 132 HKPIILGTLRNGATN 234 A0023 Der f 183 137 LGTLRNGATNHFLSK 235 A0023 Der f 184 187 GYAFIMESSSAEHEI 236 A0023 Der f 185 207 LTMLLDWRNLYPRKY 237 A0023 Der f 186 212 DWRNLYPRKYAFALP 238 A0023 Der f 187 217 YPRKYAFALPKDSQY 239 A0023 Der f 188 228 KDSQYLQHFNNAIKQ 240 A0023 Der f 189 232 LQHFNNAIKQLNTED 241 A0024 Der f/p 1057 19 NKFTVFTSGKPVSGL 242 A0024 Der f/p 1058 129 TGGISFAMEGPAKVE 243 A0024 Der f/p 1059 154 ITVIYKPPTPGDYKL 244 A0024 Der f/p 1060 164 GDYKLHLKFNDIHLP 245 A0025 Der f 2455 49 IREYRVEAIKVMLET 246 A0025 Der f 2456 54 VEAIKVMLETDRKLL 247 A0025 Der f 2457 64 DRKLLTLNNSQIILN 248 A0025 Der f 2459 74 QIILNIQYQKKKIRC 249 A0025 Der f 2462 94 LSELLTMHLLAYKQG 250 A0025 Der p 2480 148 GPHHFNVDFSKDFHN 251 A0025 Der f/p 2465 149 WSNSSAKKLLKNDID 252 A0025 Der f/p 2471 204 RSTLKLFGTIKMFMK 253 A0025 Der f/p 2472 209 LFGTIKMFMKELLDD 254 Cluster Der f 18 THFINAIVPLRQQLG 102 255 Cluster Der f 21 AIVPLRQQLGEYVDI 102 256 Cluster Der f 33 EYVDIDLVPFGNAHI 102 257 Cluster Der f 118 TGQKGFELIKVMARK 102 258 Cluster Der f 123 FELIKVMARKTPRHN 102 259 Cluster Der f 138 YVPWTTVESRTVDVN 102 260 Cluster Der f 153 VDLVKYICDNYLNNV 102 ''Der f'' denotes the species Dermatophagoides farinae ''Der p'' denotes the species Dermatophagoides pteronyssinus ''Der f/p'' denotes both species.

[0322] In each of the above sequences SEQ ID NOs: 45, 61, 63, 80, 100, 113, 147, 154, 170, 172, 191, 215, 225, 226, 248, and 260, cysteine residues (underlined and in bold typeface) may be substituted with serine, alanine or 2-aminobutyric acid; in different embodiments of SEQ ID NOs: 45 and 63, all cysteine residues may be so substituted, either exclusively with serine residues, exclusively with alanine residues, exclusively with 2-aminobutyric acid residues, or with a combination thereof.

REFERENCES

[0323] Bret, Cooper and J. Feng and W. Garrett (2010), Spectroscopy. 21 (9): 1534-1546.

[0324] Goodman R. et al, Clin Transl Allergy. 2014; 4(Suppl 2): P12

[0325] Haqqani A S et al. (2008), Methods Mol. Biol. 439: 241-56.

[0326] Henmar H et al., Clin Exp Immunol 2008; 153(3):316-23.

[0327] Ishihama Y, Oda Y, Tabata T, Sato T, Nagasu T, Rappsilber J, Mann M. Exponentially modified protein abundance index (emPAI) for estimation of absolute protein amount in proteomics by the number of sequenced peptides per protein. Mol Cell Proteomics 2005; 4: 1265-72.

[0328] Trauger A. et al. (2002), Spectroscopy. 16 (1): 15-28.

[0329] Wells W et al. (2006), Journal of Proteome Research. 5 (3): 651-658.

Example 1

[0330] This example includes a description of the identification of mite proteins extractable from mite fecal particles and/or mite bodies within a short extraction time upon being treated with neutral buffered aqueous solutions. Contrary to the relative long and more violent extraction conditions usually applied in the preparation of allergen extracts applicable for allergy immunotherapy, the present extraction conditions avoided mechanical manipulation, the extraction time was kept as short as 10 minutes and the extraction media was isotonic phosphate buffer with physiological pH. Using this extraction approach, there was identified HDM proteins releasable immediately and concurrently with known allergens, only. The short extraction time and mild extraction conditions were chosen to mimic the extraction of proteins/allergens potentially taken place on the respiratory mucosal surface in subjects exposed to mites. The identification of co-eluting proteins were then conducted using LC-MS/MS and transcriptomes of the two HDM species Der f and Der p. Homologous proteins to the Der f/Der p sequence were identified using transcriptomes of four other mite/storage mite species; Blomia tropicalis (Blo t), Glycyphagus domesticus (Gly d), Lepidoglyphus destructor (Lep d) and Tyrophagus putrescentiae (Tyr p).

[0331] Preparation of Extracts:

[0332] 10% (w/v) extracts were made using mite cultures of two different house dust mite species (Der p and Der f) and separately on the body fraction and the fecal fraction of the culture. In details, a sample of about 0.5 g was taken from each of the culture fractions and suspended in 5 ml of Phosphate buffer (PBS pH 7.2: 137 mM NaCl, 2.7 mM KCl, 8.2 mM Na.sub.2HPO.sub.4, 1.5 mM KH.sub.2PO.sub.4), and then gently rotated for 10 minutes at room temperature. Larger particles were removed by filtering through a PD10 PE bed-filter followed by removal of smaller particles through a 5 .mu.m (Millex)+a 0.8 .mu.m (Millex) filter. Filtered samples were kept on ice.

[0333] LC-MS/MS:

[0334] The four extraction samples were evaporated and 50 .mu.g of each of the dried samples was re-suspended in 5 .mu.l water. The samples were then denatured (6 M urea, 0.3 M NH4HCO3), reduced (9 mM DTT, 56.degree. C. for 15 min), alkylated (17 mM Iodoacetamide), and finally trypsin-digested (5 .mu.g trypsin at 37.degree. C., over night). Resulting peptides were then separated and analysed by liquid chromatography tandem mass spectrometry (LC-MS/MS).

[0335] Reverse phase liquid chromatography (Ultimate 3000 RSLC nano, Thermo) was performed using C18 pre- and analytical columns at a flow rate of 300 nl/min. The applied gradient consisted of a 220 min linear increase of solvent B from 4% to 55%, where solvent A=0.05% v/v formic acid and solvent B=80% v/v acetonitrile/0.04% v/v formic acid.

[0336] Peptides eluting from the LC were sprayed directly into an ESI-QTOF mass spectrometer (MaXis, Bruker). Spectra were acquired in the mass range 50-2200 m/z at 2 Hz and MS/MS sequencing at a spectral rate of 4-16 Hz.

[0337] Data Analysis:

[0338] Data processing (compound finding and charge deconvolution) was performed using DataAnalysis 4.2 (Bruker). Proteins were identified by searching the MS/MS spectral data against a database (see section below) using MASCOT 2.2 (Matrix Science) and X!Tandem search engines at the following parameters: Enzyme=trypsin, Max missed cleavages=2, Fixed modifications=carbamidomethyl (C), Variable modifications=oxidation (M), Peptide mass tolerance=10 ppm, Fragment mass tolerance .ltoreq.0.1 Da. False discovery rate (FDR) was <2% (average of 0.54%).

[0339] Database:

[0340] The database used for protein identification was compiled based on in-house transcriptomes of the two HDM species Der f and Der p as well as in-house transcriptomes of four other mite/storage mite species; Blomia tropicalis (Blo t), Glycyphagus domesticus (Gly d), Lepidoglyphus destructor (Lep d) and Tyrophagus putrescentiae (Tyr p), prepared as follows:

[0341] RNA-sequencing of all mite species was performed by UCSD using an Illumina HiSeq 2000. Sequences were assembled into transcripts including isoforms and homologs with Trinity. All transcriptomes were translated into amino acid sequences in all six reading frames. For each of the transcriptome sequences, the longest translated continuous amino acid sequence without an occurring stop codon was included in the compiled transcriptome database for the MASCOT search. A minimum length of 60 amino acids was required. Additional translated sequences from other reading frames were included if the length of the respective sequence was longer than 80% of the previously identified longest translated continuous amino acid sequence.

[0342] In addition to these transcript-derived sequences, Swissprot and Trembl sequences from the Acari subclass were also included in the database, as well as all previously identified allergens from Der f and Der p (extracted from allergen.org and allergome.org), and proteins commonly found in proteomics experiments, adding up to a database of a total of 409,187 sequences. Application of an 80% homology filter to respective species of extract origin yielded a total of 87 conserved protein groups and 438 proteins, with each group consisting of 1, 2, or more proteins. A total of 492 sequences were included in the final analysis. These sequences were clustered at a 40% identity threshold using the epitope cluster analysis tool available at IEDB into 96 clusters. Each of the 96 sequence clusters were aligned separately using the MEGA software tool (using ClustalW). Clusters corresponding to known allergens were removed from consideration, leaving a set of remaining clusters, herein named "L" clusters.

[0343] In another set of analysis, proteins were identified by conservation analysis of each translated sequence against three arachnid proteomes (Ixodes scapularis, Metaseiulus occidentalis, Stegodyphus mimosarum) derived from de novo sequence assembly. Each sequence was aligned against each proteome to identify proteins and known allergens that had >70% sequence identity over at least 50% of the length of the proteome transcript. Similar analyses were performed for each of the sequences against 1,130 proteins of the aero, bacteria, contact and venom or salivary categories from the Allergen Online Database version 15 (Goodman R. et al, Clin Transl Allergy. 2014; 4(Suppl 2): P12). Identified proteins in the samples were clustered according to a sequence homology cut off of .gtoreq.67% (historically cut off distinguishing iso-allergens from two distinct allergen groups), and a representative sequence for each cluster was selected. These clusters were named "A" clusters.

[0344] The section headed "Amino Acid Sequences" supra shows representative sequences of 22 proteins found in "L" and "A" clusters (either the Der p or the Der f sequence) and of their homologous sequences detected in either Der p, Der f and Blo t (if detected). Other homologous sequences are also found in the transcriptomes of other mites (Gly d, Lep d and Tyr p), but not reported by their sequence.

[0345] Table 1 below shows for each protein ID, the percent amino acid sequence identity between Der f and Der p homologous proteins (column 4), calculated by sequence alignment between the protein first detected in the "L" and "A" clusters (species indicated in column 2) and the homologous sequences from the other house dust mite species (species indicated in column 3); the percent amino acid sequence identity between the house dust mite protein and the homologous sequences found in humans (column 5), calculated by sequence alignment between the protein first detected in the "L" and "A" clusters (species indicated in column 2) and the human homolog protein; the percent amino acid sequence identity between the house dust mite protein and the closest homologous sequences found in Blo t by mass spectrometry (column 6), calculated by sequence alignment between the protein first detected in the "L" and "A" clusters (species indicated in column 2) and the Blo t homolog protein.

TABLE-US-00003 TABLE 1 % se- % sequence quence % sequence identity of First identity identity closest Protein detected Homolog between to human homolog ID in species f/p homolog of Blo t A0001 Der f Der p 87% No significant Not identified similarity A0003 Der f Der p 83% 38% 46% A0007 Der f Der p 90% 66% 81% A0009 Der p Der f 80% 43% 57% A0010 Der f Der p 73% 40% 54% A0011 Der f Der p 84% 30% 48% A0012 Der f Der p 92% 38% 65% A0013 Der f Der p 72% 52% 61% A0014 Der p Der f 80% 45% Not identified A0015 Der p Der f 56% 28% 32% A0016 Der f Der p 97% 74% Not identified A0017 Der f Der p 76% 35% 66% A0018 Der f Der p 91% 67% 82% A0019 Der p Der f 80% <33% 62% A0020 Der f Der p 83% 30% 44% A0022 Der p Der f 73% No significant 73% similarity A0023 Der f Der p 80% 33% Not identified A0024 Der f Der p 97% 41% 90% A0025 Der f Der p 48% No significant Not identified similarity

Example 2

[0346] This example includes a description of the immunogenicity of the proteins selected in Example 1. Immunogenicity was tested with respect to the ability of the protein or fragments of the proteins (peptides) to

[0347] stimulate reactivity of T cells obtained from mite allergic donors;

[0348] activate basophilic cells obtained from mite allergic donors; and/or

[0349] react with specific IgE and IgG antibodies of plasma from mite allergic donors.

[0350] Peptide Library:

[0351] Each sequence of an "L" cluster was aligned separately using the MEGA software tool with ClustalW. Fifteen-mer peptides overlapping by 10 amino acids were generated and the last 15-mer peptide was added when the sequence length was not divisible by 5, 14,783 unique peptides remained.

[0352] Promiscuous HLA Class II Binding Predictions and Pool Generation:

[0353] HLA class II binding predictions optimized for global coverage were performed for the seven class II alleles (HLA-DRB1*03:01, HLA-DRB1*07:01, HLA-DRB1*15:01, HLA-DRB3*01:01, HLA-DRB3*02:02, HLA-DRB4*01:01 and HLA-DRB5*01:01) using the standalone version of the IEDB class II binding prediction tool. The median consensus percentile rank was estimated from the consensus percentile ranks for the seven alleles. Further, peptides with more than ten overlapping amino acids, which appeared because several occurrences of some sequence regions were repeated multiple times in the same sequence, were eliminated (e.g. "TLSDYNIQKESTLHLVLRLRGGMQIFVKTLTG" was repeated seven times in one sequence.) Variant peptides were also removed, retaining the better peptide based on the median consensus percentile rank and conservation among the sequences within its respective cluster. Peptides with median consensus percentile rank .ltoreq.10.0 and conserved in .gtoreq.35% of sequences in the same cluster were finally selected, also including additional selected peptides chosen to maximize DRB1 allele coverage, for a grand total of 2,589 peptides.

[0354] Peptide Synthesis:

[0355] Peptides were purchased from Mimotopes (Clayton, Victoria, Australia) or A and A (San Diego, Calif.) as crude material on a small (1-mg) scale. Individual peptides were resuspended in DMSO at a final concentration of 40 mg/mL. Peptide "megapools" of 30-65 peptides/pool were generated. Following lyophilization, each pool was reconstituted in DMSO so that each peptide was present at a concentration of 4 mg/mL. To facilitate deconvolution of positive megapools, each megapool was further broken down in 2-6 "mesopools" (259 mesopools in total), each containing 8-14 peptides. Each mesopool was then deconvoluted to identify individual positive peptides. To avoid dimerization and polymerization of peptides by intra- and intermolecular disulfide bond formation between cysteine residues, this amino acid were in some instances substituted by a serine residue in the peptides. Such peptides are herein marked with an asterisk (*).

[0356] Expression of Recombinant Proteins:

[0357] Small scale recombinant proteins (>75% purity, endotoxin level<10 EU/mg) were expressed in E. coli and/or in insect cells as a custom service by GenScript (NJ, USA) using codon optimized DNA constructs. Selected proteins were further expressed in a human embryonic kidney (HEK293) suspension cell line (Freestyle.TM. 293 Expression System, Thermo Fisher, MA, USA), according to the manufacturer's instructions. Briefly: 30 .mu.g transfection grade, codon optimized plasmids encoding the protein of interest (made as a custom service by Genscript, NJ, USA), was mixed with 60 .mu.l 293Fectin.TM., and incubated for 25 min. This mixture was added to 30 ml suspension culture of HEK293 cells with a cell density of 1.10.sup.6 cell/ml. The culture was incubated in 125 ml disposable, polycarbonate, Erlenmeyer flasks with vent caps (Corning, N.Y.) in a 37.degree. C. incubator having a humidified atmosphere with 8% CO.sub.2 and orbital shaking at 125 rpm for 2-5 days before harvesting. Recombinant proteins secreted into the medium were harvested by sedimentation of the HEK293 cells at 100 g for 5 min. The cell supernatants were subsequently sterilized through a low protein binding Millex-GP 0.45 um filter (Millipore, MA, USA).

[0358] Study Population:

[0359] PBMCs from European HDM-allergic individuals were recruited in the Copenhagen region (defined by clinical history of allergy to house dust mite and specific IgE to group 1 and group 2 major allergens from Der p and/or Der f and with measured specific IgE (CAP) >0.7 kU/L towards Der p/f 1 or Der p/f 2. In addition, PBMCs from 10 US HDM-allergic individuals were recruited in San Diego (defined by Der p extract IgE titers greater than 0.35 kUA/L). PBMCs were isolated from whole blood by density gradient centrifugation according to manufacturers' instructions (Ficoll-Hypaque, Amersham Biosciences, Uppsala, Sweden). Der p- and Der f-specific extract IgE titers were determined using the ImmunoCAP system (Thermo Fisher, Uppsala, Sweden). In a separate series of experiments, pooled plasma from 10 European and 10 American HDM atopic individuals from the San Diego region, respectively, was utilized to run 2D immunoblots to elucidate IgE and IgG reactivity towards the proteins, which had at least one peptide with positive T cell response.

[0360] T Cell Reactivity of Protein:

[0361] T cells reactivity was determined by establishment of HDM specific T-cell lines according to standard methods. In short, PMBCs from HDM allergic donors were cultured for 2-3 weeks in the presence of house dust mite allergen extract. The responses to proteins having SEQ ID NOs 1-44 were assessed by IL-5/IFNg FluoroSPOT (Mabtech FS-0108-10) according manufacturer protocol, (after 2 weeks) or proliferation in a standard 72 h T cell proliferation assay, as described in Henmar H et al., Clin Exp Immunol 2008; 153(3):316-23. (after 3 weeks). In addition these established T cell lines were used for further characterization and epitope mapping.

[0362] T Cell Reactivity of Peptides:

[0363] HDM-specific T cells were expanded in vitro. Briefly, PBMCs from HDM-allergic individuals were stimulated with HDM extract (5 .mu.g/mL) and expanded over 14-17 days with IL-2 (added every 3 days). Cells were harvested on day 14, restimulated with HDM extract (5 .mu.g/mL), individual peptides (10 .mu.g/mL) or peptide pools (5 .mu.g/mL) and screened for IFN-.lamda./IL-5-production by ELISPOT. Criteria for positivity were 100 or 20 spot forming cells (SFCs) per 10.sup.6 PBMCs for peptide pools or single peptides, respectively, p<0.05, and a stimulation index >2.

[0364] Basophil Activation:

[0365] Basophil Activation Test (BAT) was used as a predictive in vitro assay for indication of safety/immediate hypersensitivity reactions. The BAT assay is a widely used diagnostic test that is also used for evaluation of allergenicity of allergen derived components. In short: whole blood from HDM allergic donors was stimulated for 1 h with the proteins, and the increased expression of activation markers on the surface of basophils were measured by flow cytometry. The BAT test was carried out using different concentrations of the proteins and the allergens Der p 2 and Der p 1 was used as controls and tested in the same concentration rates.

[0366] Determination of IqE and IqG Reactivity:

[0367] Briefly, extracts of Der p and Der f were mixed 1:1 and 300 .mu.g of extract proteins was run on 2D gels (3-10 pH range, 12% 138 (vol/vol) acrylamide) at Applied Biomics. The 2D-immunoblots of the labeled extracts were incubated with either (1) pooled plasma (diluted 1:20) from 10 HDM allergic donors recruited in San Diego or (2) pooled sera from 10 HDM allergic donors recruited in Europe (diluted 1:33). Blots were incubated with goat anti-human IgE and mouse anti-human IgG (Sigma-Aldrich), and HDM donor antibody reactivity visualized using Cy2-conjugated donkey anti-goat IgG and Cy5-conjugated donkey anti-mouse IgG antibodies (Biotium). In total 237 IgE and/or IgG-reactive protein spots were picked and analyzed by mass spectrometry by searching the MS spectra against a transcriptome sequence database. Using this database, the most likely protein of a given spot was identified. The antibody reactivity of each spot was then determined by visual inspection of the 2D-gel images. We took into account both the reactivities of the San Diego and European pools. If any spot in a given protein was antibody reactive with either cohort, the protein was considered reactive for that antibody. Then, the protein sequences from the proteomic analysis were aligned with the bioinformatically determined peptide clusters.

[0368] Table 2 shows the results obtained for the selection of 22 proteins (either the Der p of Der f protein were tested). Notably, a number of the proteins produced a T cell response in many of the tested donors, but none or a low fraction of donors had IgE reactivity towards the proteins.

TABLE-US-00004 TABLE 2 % T cell % SEQ Protein responding responding ID Cluster Cluster ID aa donors to donors in IgG IgE NO: ID (L) ID (A) name Species length protein BAT Assay reactivity reactivity 13 96 55 A0001 Der f 222 6 of 29 0 of 16 14 96 55 A0001 Der p 222 + + 2 65 74 A0003 Der f 132 3 65 74 A0003 Der p 132 1 of 29 0 of 16 - - 34 46 21 A0006 Der f 462 35 46 21 A0006 Der p 462 + - 30 61 30 A0007 Der f 361 31 61 30 A0007 Der p 362 6 of 27 0 of 8 + + 7 44 67 A0008 Der f 154 8 44 67 A0008 Der p 154 - - 43 58 6 A0009 Der f 975 44 58 6 A0009 Der p 990 7 of 24 + + 41 10 7 A0010 Der f 887 42 10 7 A0010 Der p 885 + - 39 64 16 A0011 Der f 520 40 64 16 A0011 Der p 520 15 of 27 0 of 8 - - 22 103 19 A0012 Der f 509 38 103 19 A0012 Der p 262 11 of 27 0 of 8 + - 36 40 23 A0013 Der f 463 37 40 23 A0013 Der p 474 4 of 27 0 of 8 - - 32 33 25 A0014 Der f 429 33 33 25 A0014 Der p 434 10 of 27 1 of 8* - - 26 25 34 A0015 Der f 310 27 25 34 A0015 Der p 321 1 of 24 + + 28 43 39 A0016 Der f 332 29 43 39 A0016 Der p 332 2 of 27 1 of 8* + + 21 13 49 A0017 Der f 261 25 13 49 A0017 Der p 275 3 of 26 1 of 8* - - 5 97 71 A0018 Der f 152 6 97 71 A0018 Der p 152 0 of 27 1 of 8* - - 1 75 75 A0019 Der f 130 4 75 75 A0019 Der p 134 8 of 24 - - 15 31 59 A0020 Der f 228 16 31 59 A0020 Der p 228 3 of 24 + + 19 105 50 A0022 Der f 252 20 105 50 A0022 Der p 253 6 of 24 + + 23 8 42 A0023 Der f 270 24 8 42 A0023 Der p 271 3 of 24 - - 11 36 65 A0024 Der f 188 12 36 65 A0024 Der p 188 5 of 24 - - 17 104 NA A0025 Der f 233 18 104 NA A0025 Der p 233 0 of 24 - - 9 102 62 NA Der f 171 10 102 62 NA Der p 172 + -

[0369] Table 3 shows the percentage of donors that produced a response against a peptide together with information about the source protein of the peptide (i.e. the protein with 100% sequence alignment over the peptide sequence). For example peptide with ID No: 2344 derives from protein A0001 and has 100% sequence alignment with the sequence of A0001 of Der f as well as the Der p within the stretch of consecutive amino acid residues from position 131 to 145, while peptide with ID NO: 1714 derives specifically from the Der f sequence of protein A0009 and peptide with ID NO: 1715 derives specifically from the Der p sequence of protein A0009. The peptides in the table are identical to the 15-mer peptides having SEQ ID NOs: 45-260 that are detailed in the section supra headed "Amino Acid Sequences".

TABLE-US-00005 TABLE 3 SEQ SEQ Peptide Source SFC/ % ID Peptide Source SFC/ % ID NO ID # protein donor responder NO ID # protein donor responder 45 2344 A0001 4 5% 153 2421 A0012 3 5% 46 1800 A0007 7 5% 154 2422 A0012 5 5% 47 1805 A0007 12 5% 155 2423 A0012 15 10% 48 1804 A0007 326 20% 156 2424 A0012 227 20% 49 1806 A0007 83 10% 157 2425 A0012 227 20% 50 1360 A0008 7 5% 158 2426 A0012 136 20% 51 1361 A0008 5 5% 159 2428 A0012 19 10% 52 1362 A0008 40 5% 160 2429 A0012 3 5% 53 1363 A0008 7 5% 161 2430 A0012 5 5% 54 1364 A0008 6 5% 162 2431 A0012 4 5% 55 1365 A0008 5 5% 163 2432 A0012 3 5% 56 1366 A0008 8 5% 164 2433 A0012 10 10% 57 1368 A0008 5 5% 165 2434 A0012 4 5% 58 1710 A0009 8 5% 166 2435 A0012 16 10% 59 1711 A0009 80 5% 167 2436 A0012 69 10% 60 1712 A0009 75 5% 168 2437 A0012 78 10% 61 1714 A0009 5 5% 169 2441 A0012 8 5% 62 1715 A0009 4 5% 170 2442 A0012 3 5% 63 1716 A0009 7 10% 171 2443 A0012 8 5% 64 1718 A0009 6 5% 172 2445 A0012 7 10% 65 1722 A0009 6 5% 173 1096 A0013 145 20% 66 1742 A0009 6 5% 174 1097 A0013 12 5% 67 1757 A0009 2 5% 175 1099 A0013 12 5% 68 1758 A0009 24 5% 176 1100 A0013 17 5% 69 1767 A0009 112 5% 177 1101 A0013 122 10% 70 1776 A0009 5 5% 178 1102 A0013 42 10% 71 1777 A0009 8 5% 179 1113 A0013 5 5% 72 1778 A0009 4 5% 180 1115 A0013 29 10% 73 1775 A0009 4 5% 181 1116 A0013 40 10% 74 1779 A0009 25 5% 182 1117 A0013 175 10% 75 1782 A0009 6 5% 183 1118 A0013 163 20% 76 1783 A0009 8 5% 184 1119 A0013 16 10% 77 1786 A0009 4 5% 185 1006 A0014 15 5% 78 1785 A0009 6 5% 186 1009 A0014 64 5% 79 305 A0010 5 5% 187 1012 A0014 25 10% 80 307 A0010 4 5% 188 1013 A0014 24 10% 81 306 A0010 8 5% 189 1014 A0014 24 10% 82 309 A0010 4 5% 190 1015 A0014 22 10% 83 312 A0010 4 5% 191 1016 A0014 93 20% 84 313 A0010 3 5% 192 1017 A0014 9 5% 85 314 A0010 222 20% 193 1018 A0014 19 5% 86 315 A0010 3 5% 194 1019 A0014 146 15% 87 316 A0010 69 20% 195 1020 A0014 31 10% 88 318 A0010 3 5% 196 1021 A0014 17 5% 89 321 A0010 9 5% 197 1022 A0014 21 10% 90 324 A0010 11 5% 198 1023 A0014 23 10% 91 325 A0010 9 5% 199 1024 A0014 11 5% 92 330 A0010 1 5% 200 1025 A0014 15 5% 93 331 A0010 11 10% 201 1353 A0016 8 5% 94 334 A0010 94 15% 202 404 A0017 4 5% 95 335 A0010 77 15% 203 406 A0017 2 5% 96 337 A0010 5 10% 204 407 A0017 4 5% 97 340 A0010 227 25% 205 412 A0017 44 5% 98 341 A0010 8 5% 206 413 A0017 83 10% 99 342 A0010 24 15% 207 421 A0017 6 5% 100 343 A0010 12 10% 208 425 A0017 38 5% 101 344 A0010 10 5% 209 428 A0017 7 5% 102 346 A0010 14 10% 210 2351 A0018 9 5% 103 345 A0010 69 5% 211 2352 A0018 10 5% 104 347 A0010 29 10% 212 2353 A0018 6 5% 105 348 A0010 9 5% 213 2354 A0018 9 5% 106 350 A0010 14 10% 214 2355 A0018 9 5% 107 349 A0010 9 5% 215 2065 A0019 203 30% 108 351 A0010 146 5% 216 2066 A0019 366 25% 109 352 A0010 88 25% 217 2067 A0019 229 30% 110 353 A0010 36 30% 218 2068 A0019 239 15% 111 354 A0010 19 10% 219 2069 A0019 78 5% 112 355 A0010 4 5% 220 2070 A0019 162 10% 113 356 A0010 40 15% 221 968 A0020 38 20% 114 357 A0010 35 15% 222 969 A0020 13 5% 115 358 A0010 15 20% 223 970 A0020 117 15% 116 359 A0010 30 15% 224 971 A0020 35 10% 117 360 A0010 20 20% 225 978 A0020 14 10% 118 361 A0010 37 20% 226 979 A0020 20 15% 119 362 A0010 158 10% 227 2481 A0022 26 10% 120 363 A0010 8 5% 228 2485 A0022 20 5% 121 364 A0010 8 5% 229 178 A0023 11 5% 122 365 A0010 2 5% 230 179 A0023 16 5% 123 366 A0010 149 30% 231 180 A0023 15 5% 124 367 A0010 20 10% 232 181 A0023 5 5% 125 368 A0010 5 5% 233 182 A0023 5 5% 126 375 A0010 72 15% 234 183 A0023 8 5% 127 373 A0010 7 10% 235 184 A0023 10 5% 128 374 A0010 10 10% 236 185 A0023 11 5% 129 377 A0010 24 20% 237 186 A0023 10 5% 130 378 A0010 55 5% 238 187 A0023 8 5% 131 380 A0010 160 25% 239 188 A0023 119 15% 132 379 A0010 44 15% 240 189 A0023 15 10% 133 381 A0010 47 5% 241 1057 A0024 16 5% 134 382 A0010 4 5% 242 1058 A0024 11 5% 135 383 A0010 3 5% 243 1059 A0024 16 5% 136 384 A0010 2 5% 244 1060 A0024 8 5% 137 369 A0010 41 10% 245 2455 A0025 10 5% 138 332 A0010 3 5% 246 2456 A0025 13 10% 139 1859 A0011 16 10% 247 2457 A0025 18 10% 140 1860 A0011 55 5% 248 2459 A0025 6 5% 141 1861 A0011 7 5% 249 2462 A0025 14 10% 142 1862 A0011 22 10% 250 2480 A0025 55 10% 143 1863 A0011 11 10% 251 2465 A0025 6 5% 144 1865 A0011 10 10% 252 2471 A0025 14 10% 145 1866 A0011 228 30% 253 2472 A0025 9 5% 146 1867 A0011 54 20% 254 Cluster 88 10% 102 147 1868 A0011 28 20% 255 Cluster 72 10% 102 148 1870 A0011 21 10% 256 Cluster 417 15% 102 149 1871 A0011 12 10% 257 Cluster 604 15% 102 150 1880 A0011 21 5% 258 Cluster 316 15% 102 151 1881 A0011 9 5% 259 Cluster 52 20% 102 152 1882 A0011 5 5% 260 Cluster 50 10% 102

Example 3

[0370] This example relates to the further testing of immunogenicity of the proteins identified in Example 1. Their ability to react with IgE antibodies in HDM allergic individuals, to stimulate in vitro T cell proliferation of HDM allergic individuals and non-allergics, and to stimulate ex vivo cytokine production of HDM allergic individuals and non-allergics. The following tests were used:

[0371] Basophil Activation Test (BAT) was used as a predictive in vitro assay for indication of safety/immediate hypersensitivity reactions. BAT test was carried out using blood from HDM allergic individuals (n=14), and by use of different concentrations of test proteins or or the major house dust mite allergens (Der p 1, Der f 1, Der p 2 or Der f 2, e.g. a concentration of 1, 10, 100 or 1000 ng/ml.

[0372] In vitro T cell reactivity determined in T cell lines obtained from HDM allergic individuals (n=30) and non-allergics (n=8): Determined by establishment of HDM specific T-cell lines according to standard methods. In short, PMBCs from HDM allergic donors were cultured for 3 weeks in the presence of house dust mite allergen extract. The responses to proteins at a concentration of 0.5 ug/ml or 2 ug/ml of the test protein or the major house dust mite allergens (Der p 1, Der f 1, Der p 2 or Der f 2) were assessed by proliferation in a standard 72 h T cell proliferation assay, as described in Henmar H et al., Clin Exp Immunol 2008; 153(3):316-23. T cell reactivity was.

[0373] Ex vivo stimulation of PBMC cells obtained from mite allergic patients (n=16) and non-allergics (n=6): Determined by measuring the production of the cytokines; IFN-gamma, IL-9, IL-10, IL-17 and IL-31 following stimulation with test protein in concentration up to 10 ug/ml. Freshly isolated PBMC 5.times.10.sup.6/ml were cultured with a test protein for 5 days and cell supernatant were harvested and stored at -80.degree. C. Cytokines of the supernatants were measured using ProcartaPlex Multiplex Immunoassays with MAGPIX Multiplex Reader according manufactory protocol.

TABLE-US-00006

[0373] TABLE 4 % responders # of individuals of 14 with of in-vitro T cell positive BAT test proliferation test Test 10 Non- protein 1 ng/ml ng/ml 100 ng/ml 1000 ng/ml Allergic allergics A001 0 0 1 2 17 0 A003 0 0 0 1 3 0 A007 0 0 0 0 21 38 A009 0 0 0 3 36 63 A010 0 0 0 1 100* 14 A011 0 0 0 1 64 13 A012 0 0 0 0 39 13 A013 0 0 0 0 18 13 A014 0 0 0 0 43 0 A015 0 0 0 0 4 0 A016 0 0 0 0 7 0 A017 0 0 0 0 7 0 A018 0 0 0 0 0 0 A019 2 2 2 4 39 13 A020 0 1 1 1 18 25 A022 0 0 3 5 29 0 A023 1 1 1 1 21 0 A024 2 2 3 3 21 0 A025 1 1 1 5 0 0 A026 1 1 1 2 54 71 Derfl 10 10 10 10 70 0 Derf2 13 13 13 13 67 14 Derpl 7 10 10 10 73 13 Derp2 13 13 13 13 57 0 *A010 were only tested in T-cell lines from 3 allergic donors, all responsive.

[0374] Comments: Overall, the test proteins identified in Example 1, did only provide a positive BAT test in none or a very few mite allergic individuals, whereas they stimulated T cell proliferation in a larger percentage of the mite allergic individuals. In contrast, the major allergens produce both positive BAT test and stimulates T cell proliferation in a significant larger fraction of the mite allergic individuals.

TABLE-US-00007 TABLE 5 % HDM allergic individuals with cytokine % non-allergic individuals with cytokine Test production in ex-vivo T cell assay production in ex-vivo T cell assay protein IL-5 IL-9 IL-13 INF-g IL-10 IL-17 IL-31 IL-5 IL-9 IL-13 INF-g IL-10 IL-17 IL-31 A001 6 0 6 6 75 25 0 0 0 0 0 100 50 0 A003 6 0 13 0 19 13 0 0 0 0 0 17 17 0 A007 6 6 19 31 44 38 0 0 0 0 33 83 67 0 A009 0 0 6 19 94 19 0 0 0 0 50 100 33 0 A010 31 13 44 0 38 13 6 0 0 0 0 0 0 0 A011 25 6 19 0 13 6 6 0 0 0 17 0 0 0 A012 69 25 44 0 19 19 0 0 0 0 17 67 33 0 A013 50 25 38 0 38 6 0 0 0 0 0 0 0 0 A014 6 0 6 13 25 31 0 0 0 0 33 33 33 0 A015 6 0 6 25 75 44 6 0 0 0 33 67 50 0 A016 6 0 13 6 25 13 0 0 0 0 0 0 17 0 A017 0 0 0 6 25 13 0 0 0 0 0 33 17 0 A018 0 6 13 19 56 44 6 0 0 17 33 67 83 0 A019 38 56 56 50 75 100 13 0 0 0 100 100 100 17 A020 6 0 6 0 25 6 0 0 0 0 17 0 0 0 A022 31 6 13 0 6 0 0 0 0 0 17 0 0 0 A023 13 13 13 0 6 0 0 0 0 0 0 0 0 0 A024 13 6 6 0 25 6 0 0 0 0 0 17 0 0 A025 13 6 13 0 6 0 0 0 0 0 0 0 0 0 A026 44 25 44 0 38 0 0 0 0 0 0 50 17 0 Derf1 75 19 56 0 50 6 0 0 0 0 0 33 17 0 Derf2 63 50 69 6 81 13 6 0 0 0 17 33 67 0 Derp1 50 6 50 0 50 6 0 0 0 0 0 17 17 0 Derp2 56 31 50 0 56 0 6 0 0 0 0 17 0 0

Example 4

[0375] This example relates to the abundance of the proteins in house dust mite extracts relatively to the abundance of known allergens of house dust mite extracts.

[0376] The abundance was determined as follows: MS/MS spectra were searched (via MASCOT search engine, Matrix Science) against an in-house allergen database that included the protein sequences of all novel proteins A0001-A0025 as well as all known HDM allergens group 1-35. The sum of the relative and semi-quantitative Exponentially Modified Protein Abundance Index (emPAI) scores (Ishihama Y et al. 2005) of all hits were set to 100%, and the relative percentage (molar %) of each protein was calculated. The abundance of the known HDM allergens is shown as one pooled result.

[0377] Table 6 shows the relative abundance of the novel proteins and known HDM allergens

TABLE-US-00008 TABLE 6 Der p Der f bodies Der p fecals bodies, Mild Der f fecals Mild extraction Mild extraction Der p full extraction Mild extraction Der f full Protein (10 min) (10 min) extract (10 min) (10 min) extract HDM 64.2 88.5 50.1 50.8 47.3 51.2 allergens A0001 5.0 0.5 4.5 8.0 11.6 9.2 A0003 3.9 <0.0 17.8 19.0 11.9 13.5 A0006 0.6 0.5 0.7 1.2 0.6 0.7 A0007 1.3 0.3 2.1 4.5 2.4 3.5 A0008 2.0 0.8 4.8 4.2 3.4 4.7 A0009 1.0 0.3 0.6 2.3 0.6 0.4 A00010 0.8 0.5 0.6 2.0 0.3 1.1 A00011 <0.0 <0.0 0.2 0.4 <0.0 0.4 A00012 <0.0 <0.0 <0.0 <0.0 <0.0 0.2 A00013 <0.0 <0.0 <0.0 0.4 1.0 <0.0 A00014 4.0 0.5 0.7 0.8 <0.0 0.9 A00015 2.5 0.3 1.4 <0.0 <0.0 <0.0 A00016 0.4 <0.0 2.4 0.6 4.2 4.8 A00017 <0.0 <0.0 <0.0 <0.0 1.2 0.4 A00018 3.7 0.9 4.1 4.8 11.3 2.6 A00019 6.3 5.3 1.8 <0.0 <0.0 <0.0 A00020 <0.0 0.5 1.5 <0.0 1.3 0.9 A00022 4.2 1.0 1.3 <0.0 <0.0 <0.0 A00023 <0.0 <0.0 <0.0 <0.0 1.1 0.8 A00024 <0.0 <0.0 5.3 1.0 1.8 2.9 A00025 <0.0 <0.0 <0.0 <0.0 <0.0 1.9

Sequence CWU 1

1

3321130PRTDermatophagoides farinae 1Asp Gly Ser His Ile Val Lys Ala Ala Arg Ser Gln Ile Gly Val Pro1 5 10 15Tyr Ser Trp Gly Gly Gly Gly Ile His Gly Lys Ser Lys Gly Ile Gly 20 25 30Glu Gly Ala Asn Ile Val Gly Phe Asp Cys Ser Gly Leu Ala Gln Tyr 35 40 45Ser Ile Tyr Gln Gly Thr His Lys Thr Ile Ala Arg Thr Ala Ala Ala 50 55 60Gln Tyr Asn Asp Asn His Cys His His Val Ala Tyr Gly Ser His Gln65 70 75 80Pro Gly Asp Leu Val Phe Phe Gly Asn Pro Ile Tyr His Val Gly Ile 85 90 95Val Ser Ala His Gly Arg Met Val Asn Ala Pro Lys Pro Gly Thr Lys 100 105 110Val Arg Glu Glu Asn Ile Trp Ser Tyr His Ile Ser His Val Ala Arg 115 120 125Cys Trp 1302132PRTDermatophagoides farinae 2Met Ala Ile Asp Gly Lys Tyr Gln Met Glu Ser Ser Glu His Phe Glu1 5 10 15Glu Phe Val Lys Glu Met Gly Leu Asp Val Asp Met Thr Asn Val Asp 20 25 30Leu Ser Lys Thr Ser Thr Met Glu Ile Cys Lys Asp Gly Asp Val Tyr 35 40 45His Ile Lys Ser Glu Thr Ala Gly Ile Ala His Glu Ile Lys Phe Lys 50 55 60Val Gly Glu Glu Phe Glu Asp Asp Met Asn Gly His Lys Phe Lys Asn65 70 75 80Val Val Thr Met Glu Cys Asp Asn Lys Met Val Gln Lys Lys Thr Ser 85 90 95Ala Asp Gly Gly Lys Val Val Asn Val Val Arg Glu Phe Thr Asp Ala 100 105 110Gly Cys Thr Val Lys Ser Thr Tyr Asn Thr Val Thr Trp Thr Arg Val 115 120 125Tyr Lys Arg Met 1303132PRTDermatophagoides pteronyssinus 3Met Ala Ile Asp Gly Lys Tyr Gln Met Glu Ser Ser Glu His Phe Glu1 5 10 15Glu Phe Val Lys Glu Met Gly Leu Asp Val Asp Met Thr Asn Val Asp 20 25 30Leu Ser Lys Thr Ser Thr Met Glu Ile Cys Lys Asp Gly Asp Val Tyr 35 40 45His Ile Lys Ser Glu Thr Ala Gly Ile Ala His Glu Ile Lys Phe Lys 50 55 60Val Gly Glu Glu Phe Glu Asp Asp Met Asn Gly His Lys Phe Lys Asn65 70 75 80Val Val Thr Met Glu Cys Asp Asn Lys Met Val Gln Lys Lys Thr Ser 85 90 95Ala Asp Gly Gly Lys Val Val Asn Val Val Arg Glu Phe Thr Asp Ala 100 105 110Gly Cys Thr Val Lys Ser Thr Tyr Asn Thr Val Thr Trp Thr Arg Val 115 120 125Tyr Lys Arg Met 1304134PRTDermatophagoides pteronyssinus 4Gln Val Tyr Cys Asn Gly Ala Ala Ile Val Ser Ala Ala Arg Ser Gln1 5 10 15Ile Gly Val Pro Tyr Ser Trp Gly Gly Gly Gly Ile His Gly Lys Ser 20 25 30Arg Gly Ile Gly Glu Gly Ala Asn Thr Val Gly Phe Asp Cys Ser Gly 35 40 45Leu Ala Gln Tyr Ser Val Tyr Gln Gly Thr His Lys Val Leu Ala Arg 50 55 60Val Ala Ser Gly Gln Tyr Ser Asp Pro Lys Cys His His Val Ala Tyr65 70 75 80Gly Ser His Gln Pro Gly Asp Leu Val Phe Phe Gly Asn Pro Ile His 85 90 95His Val Gly Ile Val Ser Ala His Gly Arg Met Ile Asn Ala Pro His 100 105 110Thr Gly Thr Asn Val Arg Glu Glu Asn Ile Trp Ser Asp His Ile Ala 115 120 125Asn Val Ala Arg Cys Trp 1305152PRTDermatophagoides farinae 5Met Val Lys Ala Val Val Val Leu Lys Gly Glu Pro Asn Val Thr Gly1 5 10 15Thr Ile Phe Phe Glu Gln Gln Asp Asn Gly Pro Val Lys Val Ser Gly 20 25 30Thr Val Gln Gly Leu Lys Ser Gly Leu His Gly Phe His Val His Glu 35 40 45Phe Gly Asp Asn Thr Asn Gly Cys Thr Ser Ala Gly Ala His Tyr Asn 50 55 60Pro Phe Asn Lys Thr His Gly Ala Pro Ala Asp Glu Glu Arg His Val65 70 75 80Gly Asp Leu Gly Asn Val Glu Ala Asn Asp Ala Gly Ile Ala Asn Val 85 90 95Ala Ile Glu Asp Ser Leu Ile Ser Leu Thr Gly Glu Arg Ser Ile Val 100 105 110Gly Arg Ser Leu Val Val His Ala Asp Pro Asp Asp Leu Gly Arg Gly 115 120 125Gly His Glu Leu Ser Lys Thr Thr Gly Asn Ala Gly Gly Arg Leu Ala 130 135 140Cys Gly Val Ile Gly Val Thr Lys145 1506152PRTDermatophagoides pteronyssinus 6Met Val Lys Ala Val Val Val Leu Lys Gly Asp Pro Asn Val Ser Gly1 5 10 15Thr Ile Phe Phe Glu Gln Gln Asp Asn Gly Pro Val Lys Val Thr Gly 20 25 30Ser Val Gln Gly Leu Lys Pro Gly Leu His Gly Phe His Val His Glu 35 40 45Phe Gly Asp Asn Thr Asn Gly Cys Thr Ser Ala Gly Ala His Tyr Asn 50 55 60Pro Leu Asn Lys Thr His Gly Ala Pro Asn Asp Glu Glu Arg His Val65 70 75 80Gly Asp Leu Gly Asn Ile Glu Ala Asn Asp Lys Gly Val Ala Asn Val 85 90 95Val Ile Glu Asp Ser Leu Ile Ser Leu Thr Gly Glu Lys Ser Ile Val 100 105 110Gly Arg Ser Leu Val Val His Ala Asp Pro Asp Asp Leu Gly Arg Gly 115 120 125Gly His Glu Leu Ser Lys Thr Thr Gly Asn Ala Gly Gly Arg Leu Val 130 135 140Cys Gly Val Ile Gly Val Thr Lys145 1507154PRTDermatophagoides farinae 7Met Ser Ala Asn Thr Glu Arg Thr Phe Ile Met Leu Lys Pro Asp Ala1 5 10 15Val Gln Arg Gly Ile Val Gly Glu Ile Ile Arg Arg Phe Glu Ala Lys 20 25 30Gly Phe Lys Leu Val Ala Met Lys Phe Met Met Ala Ser Glu Asp Leu 35 40 45Leu Lys Lys His Tyr Ala Asp Leu Ala Ala Arg Pro Phe Phe Pro Gly 50 55 60Leu Ile Lys Tyr Met Gln Met Gly Pro Val Val Pro Met Val Trp Glu65 70 75 80Gly Leu Asn Ala Val Lys Thr Gly Arg Val Met Leu Gly Glu Thr Asn 85 90 95Pro Ala Glu Ser Lys Pro Gly Thr Ile Arg Gly Asp Leu Cys Ile Gln 100 105 110Thr Gly Arg Asn Ile Ile His Gly Ser Asp Ser Val Glu Thr Ala Lys 115 120 125Arg Glu Ile Asp Leu Trp Phe Arg Pro Glu Glu Leu Val Asp Tyr Lys 130 135 140Pro Ser Gln Tyr Glu Trp Val Tyr Glu Asn145 1508154PRTDermatophagoides pteronyssinus 8Met Ser Ala Asn Thr Glu Arg Thr Phe Ile Met Leu Lys Pro Asp Ala1 5 10 15Val Gln Arg Gly Ile Val Gly Glu Ile Ile Arg Arg Phe Glu Ala Lys 20 25 30Gly Phe Lys Leu Val Ala Met Lys Phe Met Met Ala Ser Glu Asp Leu 35 40 45Leu Lys Lys His Tyr Ala Asp Leu Ala Ala Arg Pro Phe Phe Pro Gly 50 55 60Leu Ile Lys Tyr Met Gln Met Gly Pro Val Val Pro Met Val Trp Glu65 70 75 80Gly Leu Asn Ala Val Lys Thr Gly Arg Val Met Leu Gly Glu Thr Asn 85 90 95Pro Ala Glu Ser Lys Pro Gly Thr Ile Arg Gly Asp Leu Cys Ile Gln 100 105 110Thr Gly Arg Asn Ile Ile His Gly Ser Asp Ser Val Glu Thr Ala Lys 115 120 125Arg Glu Ile Asp Leu Trp Phe Arg Pro Glu Glu Leu Val Asn Tyr Lys 130 135 140Pro Ser Gln Tyr Glu Trp Val Tyr Glu Asn145 1509171PRTDermatophagoides farinae 9Asn Arg Val Ser Val Gly Val Tyr Tyr Glu Thr Ile Cys Ser Gly Cys1 5 10 15Arg Thr His Phe Ile Asn Ala Ile Val Pro Leu Arg Gln Gln Leu Gly 20 25 30Glu Tyr Val Asp Ile Asp Leu Val Pro Phe Gly Asn Ala His Ile Tyr 35 40 45Ser Asn Gly Pro Gln Cys Gln His Gly Ala Leu Glu Cys Tyr Gly Asn 50 55 60Ala Phe Gln Ala Cys Ser Leu Asp Met Asn Gly Phe Asp Thr Gly Phe65 70 75 80Lys Leu Val Glu Cys Met Phe Arg Ser Ser Tyr Tyr Ser Asn Pro Gln 85 90 95Tyr Ser Ala Lys Arg Cys Ala Gln Gln Leu Asn Leu Asn Tyr Asp Gln 100 105 110Leu His Ser Cys Ala Thr Gly Gln Lys Gly Phe Glu Leu Ile Lys Val 115 120 125Met Ala Arg Lys Thr Pro Arg His Asn Tyr Val Pro Trp Thr Thr Val 130 135 140Glu Ser Arg Thr Val Asp Val Asn Val Asp Leu Val Lys Tyr Ile Cys145 150 155 160Asp Asn Tyr Leu Asn Asn Val Pro Ala Cys Asn 165 17010172PRTDermatophagoides pteronyssinus 10Thr Gln Arg Val Thr Val Gly Val Tyr Tyr Glu Thr Ile Cys Pro Gly1 5 10 15Cys Arg Ser His Phe Ile Gln Ala Ile Val Pro Leu Lys Asn Gln Leu 20 25 30Gly Gln Tyr Val Asn Ile Asp Leu Val Pro Phe Gly Asn Ala His Phe 35 40 45Tyr Ser Asn Gly Pro Gln Cys Gln His Gly Gln Leu Glu Cys Tyr Gly 50 55 60Asn Ala Phe Gln Ala Cys Ser Leu Asp Met Asn Gly Phe Glu Thr Ala65 70 75 80Phe Lys Leu Val Glu Cys Met Phe Arg Ser Asn Tyr Phe Ser Asn Pro 85 90 95Glu Tyr Ser Ser Lys Gln Cys Ser Gln Gln Leu Asn Leu Asp Tyr Gln 100 105 110Gln Leu Asp Ser Cys Ala Asn Gly Gln Lys Gly Leu Gln Leu Ile Arg 115 120 125Glu Met Ala Asn Lys Thr Pro Ser His Gln Tyr Val Pro Trp Thr Thr 130 135 140Val Gln Gly Arg Phe Val Asp Gly Asn Val Asp Leu Val Asp Tyr Ile145 150 155 160Cys Glu Asn Tyr Leu Asn Gly Val Pro Ala Cys Asn 165 17011188PRTDermatophagoides farinae 11Met Ser Ile Ser Ala His Gly Gly Gly Leu Val Asn Gly Ile Ala Gly1 5 10 15Met Glu Asn Lys Phe Thr Val Phe Thr Ser Gly Lys Pro Val Ser Gly 20 25 30Leu Thr Val Ala Phe Glu Gly Pro Thr Lys Pro Glu Ile Asn Phe Asn 35 40 45Ser Thr Lys Asp Gly Ser Val Asp Val Gly Tyr Thr Pro Lys Ala Gly 50 55 60Gly Gln Tyr Lys Ile His Ile Lys Tyr Glu Gly Lys Glu Ile Val Gly65 70 75 80Ser Pro Phe Lys Cys Asn Ile Ser Gly Asp Glu Ala Thr His Arg Lys 85 90 95Leu Thr Glu Lys Val Lys Val Gly Gly Pro Asn Ile Asn Ala Gly Lys 100 105 110Val Asn Gln Asp Asn Gln Leu Thr Ile Asp Cys Lys Glu Ala Gly Ile 115 120 125Thr Gly Gly Ile Ser Phe Ala Met Glu Gly Pro Ala Lys Val Glu Val 130 135 140Ser Phe Arg Asn Asn Asn Asp Gly Thr Ile Thr Val Ile Tyr Lys Pro145 150 155 160Pro Thr Pro Gly Asp Tyr Lys Leu His Leu Lys Phe Asn Asp Ile His 165 170 175Leu Pro Gly Ser Pro Tyr Pro Ile Val Val Ala Ala 180 18512188PRTDermatophagoides pteronyssinus 12Met Ser Ile Ser Ala His Gly Gly Gly Leu Val Asn Gly Ile Ala Gly1 5 10 15Met Glu Asn Lys Phe Thr Val Phe Thr Ser Gly Lys Pro Val Ser Gly 20 25 30Leu Thr Val Ala Phe Glu Gly Pro Thr Lys Pro Glu Ile Asn Phe Asn 35 40 45Ser Thr Lys Asp Gly Ser Val Asp Val Gly Tyr Ile Pro Lys Ala Gly 50 55 60Gly Gln Tyr Lys Ile His Ile Lys Tyr Glu Gly Lys Glu Ile Val Gly65 70 75 80Ser Pro Phe Lys Cys Asn Ile Ser Gly Asp Glu Ser Thr His Arg Lys 85 90 95Leu Thr Glu Lys Val Lys Val Gly Gly Pro Asn Ile Ser Thr Gly Lys 100 105 110Val Asn Gln Asp Asn Gln Leu Thr Ile Asp Cys Lys Glu Ala Gly Ile 115 120 125Thr Gly Gly Ile Ser Phe Ala Met Glu Gly Pro Ala Lys Val Glu Val 130 135 140Ser Phe Arg Asn Asn Asn Asp Gly Thr Ile Thr Val Ile Tyr Lys Pro145 150 155 160Pro Thr Pro Gly Asp Tyr Lys Leu His Leu Lys Phe Asn Asp Ile His 165 170 175Leu Pro Gly Ser Pro Tyr Pro Ile Val Val Ser Ala 180 18513222PRTDermatophagoides farinae 13Lys Lys Thr Lys Asp Cys Asp Val Glu Lys Pro Ile Arg Glu Cys Leu1 5 10 15Lys Asn Gly Leu Leu Arg Tyr Ser Asp Gly Gln Lys Ile Asn Gln Phe 20 25 30Pro Asp Ser Ile Glu Asp Leu Asn Arg Ala Cys Glu Glu Leu Lys Lys 35 40 45Ser Glu Thr Cys Ala Arg Asn Phe Ile Asp Thr Cys Thr Glu Thr Ser 50 55 60Tyr Glu Lys Arg Ser Leu Asp Ser Leu Leu Asp Gly Ile Gln Arg Val65 70 75 80Leu Lys Arg Leu Cys Arg Ser Gln Ser Lys Lys Glu Gln Leu Leu Gln 85 90 95Asn Val Gly Cys Ala Asn Ser Val Val Gln Asp Thr Lys Leu Cys Leu 100 105 110Lys Asn Tyr Arg Met Leu Val Phe Ala Ala Asn Lys Leu Asn Asp Lys 115 120 125Ser Lys Ile Met Arg Ile Leu Cys Cys Lys Ser Arg Lys Val Ala Pro 130 135 140Cys Ile Gly Glu Ala Met Lys Ser Lys Gly Asn Ala Val Cys Ser Ala145 150 155 160Lys Asn Ile Asp Tyr Phe Arg Glu Met His Gln Asn Ile Lys Ala Glu 165 170 175Met Thr Ala Val Val Cys Ser Asp Phe Glu Arg Asp Gln Cys Glu Asn 180 185 190Val Glu Val Pro Ala Ile Thr Glu Ala Glu Tyr Lys Asp Gln Asn Ile 195 200 205Phe Asn Pro Leu Arg Asp Leu Tyr Lys Lys Val Ile Leu Ala 210 215 22014222PRTDermatophagoides pteronyssinus 14Lys Lys Ser Pro Asp Cys Asp Ile Glu Arg Pro Ile Arg Glu Cys Leu1 5 10 15Lys Asp Gly Leu Leu Arg Tyr Ser Ser Gly Gln Lys Ile Asn Gln Phe 20 25 30Pro Asp Thr Ile Gln Asp Leu Asn Arg Ala Cys Glu Glu Leu Lys Lys 35 40 45Ser Glu Thr Cys Ala Arg Thr Phe Ile Asp Thr Cys Thr Glu Ser Ser 50 55 60Tyr Glu Lys Arg Ser Leu Asp Ser Leu Leu Asp Gly Ile Gln Arg Val65 70 75 80Met Lys Arg Leu Cys Arg Ser Gln Thr Lys Lys Glu Lys Leu Leu Glu 85 90 95Asn Val Gly Cys Ala Asn Ser Val Val Gln Asp Thr Lys Gln Cys Leu 100 105 110Lys Asn Tyr Arg Met Leu Val Phe Ala Ala Asn Lys Leu Asp Asn Lys 115 120 125Asn Lys Ile Met Arg Ile Leu Cys Cys Lys Ser Arg Lys Val Ala Pro 130 135 140Cys Ile Gly Glu Ala Met Lys Ala Lys Gly Thr Ala Val Cys Ser Ala145 150 155 160Lys Asn Ile Asp Tyr Phe Lys Asp Val His Gln Asn Ile Lys Gln Glu 165 170 175Met Thr Ala Val Val Cys Ser Asp Phe Glu Arg Asp Gln Cys Glu Asn 180 185 190Val Asp Val Pro Asn Ile Ser Glu Ser Glu Tyr Lys Asp Gln Asn Ile 195 200 205Phe Asn Pro Leu Arg Asp Leu Tyr Lys Lys Val Ile Leu Gly 210 215 22015228PRTDermatophagoides farinae 15Met Ser Lys Pro Thr Phe Tyr Phe His Pro Phe Ser Gly Pro Cys Arg1 5 10 15Thr Val Ser Thr Val Ala Lys Ile Leu Asn Val Glu Met Glu Met Lys 20 25 30Lys Leu Asp Leu Leu Thr Gln Glu His Leu Lys Pro Glu Phe Leu Lys 35 40 45Val Asn Pro Phe His Lys Ile Pro Thr Phe Val Asp Thr Asp Gly Phe 50 55 60Thr Ile Asp Glu Ser Arg Val Ile Ala Met Tyr Leu Leu Gln Ser Arg65 70 75 80Lys Pro Asp Ser Phe Leu Tyr Pro Asn Asn Asp Leu Lys Lys Arg Thr 85 90 95Gln Ile Asp Arg Trp Leu His Tyr Asp Ile Ser Phe Ala Thr Ile Ile 100 105 110Ser Thr Pro

Met Tyr Cys Lys Phe Arg Gly Lys Pro Val Gln Asp His 115 120 125Gln Val Glu Gln Gly Lys Glu Thr Leu Lys Thr Leu Asp Gly Val Met 130 135 140Ala Ser Phe Gly Gly Lys Phe Leu Thr Gly Ser Asp Gln Ile Thr Leu145 150 155 160Ala Asp Ile Ala Met Tyr Phe Ser Cys Asn Thr Met Glu Ile Tyr Ser 165 170 175Glu Tyr Phe Lys Phe Asp Asp Tyr Pro Asn Leu Lys Ser Trp Tyr Gln 180 185 190Arg Val Ala Glu Ala Leu Lys Gln Tyr Asp Thr Glu Gly Glu Ile Pro 195 200 205Lys Ala Ile Glu Met Ile Lys Gln Phe Ala Gln Gln Arg Met Ala Glu 210 215 220Ser Ala Lys Gln22516228PRTDermatophagoides pteronyssinus 16Met Ser Lys Pro Ile Phe Tyr Tyr His Pro Phe Ser Gly Pro Cys Arg1 5 10 15Thr Val Ser Thr Val Ala Lys Ile Leu Asn Val Asp Met Glu Met Lys 20 25 30Lys Leu Asp Leu Leu Thr Lys Glu His Leu Asn Pro Glu Phe Leu Lys 35 40 45Val Asn Pro Phe His Lys Val Pro Thr Phe Val Asp Ser Asp Gly Phe 50 55 60Val Val Asp Glu Ser Arg Val Ile Ala Met Tyr Leu Val Glu Ser Arg65 70 75 80Lys Pro Asp Ser Phe Leu Tyr Pro Lys Asn Asp Leu Lys Lys Arg Ile 85 90 95Gln Ile Asp Arg Trp Leu His Tyr Asp Ile Asn Leu Ser Thr Thr Ile 100 105 110Ser Ala Pro Met Phe Cys Val Phe Arg Gly His Gln Val Gln Asp Tyr 115 120 125Gln Val Glu Gln Gly Lys Glu Thr Leu Lys Thr Leu Asp Gly Val Met 130 135 140Gln Ser Phe Glu Gly Lys Phe Leu Thr Gly Ala Asp Gln Phe Thr Leu145 150 155 160Ala Asp Ile Ala Met Tyr Phe Ser Leu Asn Thr Met Glu Val Tyr Pro 165 170 175Lys Tyr Phe Lys Phe Asp Asp Tyr Pro Asn Leu Lys Ser Trp Tyr His 180 185 190Arg Val Ala Glu Ala Leu Lys Gln Tyr Asp Thr Glu Gly Thr Ile Pro 195 200 205Lys Ala Ile Glu Thr Met Lys Gln Phe Ile Gln Gln Arg Ala Ala Glu 210 215 220Ala Glu Lys His22517233PRTDermatophagoides farinae 17Glu Ser Leu Phe Ile Tyr Asp Asp Tyr Ser Cys Gly Ser Tyr Gly His1 5 10 15Asp Val Asn Glu Leu Ile Glu Gln Phe Gln Leu Phe Lys Lys Asn Glu 20 25 30His Asn Gln Asn Glu Ser Ile Glu Ile Ile Gly His Phe Leu Lys Lys 35 40 45Ile Arg Glu Tyr Arg Val Glu Ala Ile Lys Val Met Leu Glu Thr Asp 50 55 60Arg Lys Leu Leu Thr Leu Asn Asn Ser Gln Ile Ile Leu Asn Ile Gln65 70 75 80Tyr Gln Lys Lys Lys Ile Arg Cys Glu Asn Leu Lys His Leu Ser Glu 85 90 95Leu Leu Thr Met His Leu Leu Ala Tyr Lys Gln Gly Met Phe Asp Phe 100 105 110Ala Glu Glu Ile Asp Pro Asp Val Asn Phe Asp Arg Gln Phe Lys Asn 115 120 125Phe Leu Asp Arg Ser Ser Glu Val Met Asn Ile Asn Glu Phe Ser Asp 130 135 140Ile Glu Lys Lys Trp Ser Asn Ser Ser Ala Lys Lys Leu Leu Lys Asn145 150 155 160Asp Ile Asp Gly Leu Ile Thr Ala Leu Asp Asp Leu Arg Glu Asp Phe 165 170 175Leu Lys Asn Ile Ile Leu Pro Glu Phe Asp Ala Gln Ser Arg Tyr Asp 180 185 190Leu Tyr Phe Ser Ile Gln Asp Gln Ile Asn Ile Arg Ser Thr Leu Lys 195 200 205Leu Phe Gly Thr Ile Lys Met Phe Met Lys Glu Leu Leu Asp Asp Leu 210 215 220Asn Gln Pro Asp Phe Glu Ile Leu Tyr225 23018229PRTDermatophagoides pteronyssinus 18Gln Ser Leu Phe Val Asp Tyr Asn Asp Tyr Ser Cys Gly Ser Ser Gln1 5 10 15Asn Glu Thr Asn Glu Leu Ile Gln Glu Phe Lys Ile Phe Lys Lys Asn 20 25 30Ile Asn Gly Asn Glu Asn Phe Lys Lys Ile Asn Asp Phe Ile Glu Lys 35 40 45Ala Arg Leu Phe Arg Asp Asn Ala Ala Lys Gln Met Leu Glu Ile Asp 50 55 60Gln Gln Leu Leu Thr Leu Asn Val Ile Gln Ile Ser Gln Arg Ile Lys65 70 75 80Leu Glu Asn Asn Lys Ile Gln Cys Glu Lys Leu Thr Lys Phe Ser Glu 85 90 95Leu Leu Ser Met Gln Leu Leu Ala Tyr Glu Val Gly Met Phe Glu Phe 100 105 110Ala Glu Glu Ile Asp Pro Asn Ile Asp Phe Asp Arg Lys Met Lys Asn 115 120 125Phe Leu Asp Glu Thr Ser Arg Leu Phe Asn Leu Ala Glu Phe Glu Lys 130 135 140Leu Glu Lys Lys Phe Arg Asn Ala Thr Ser Ile Glu Lys Leu Lys Asn145 150 155 160Tyr Ile Asp Gly Glu Leu Val Ala Leu Asn Asp Tyr Ile Asn Glu Phe 165 170 175Leu Lys Asp Ile Ile Met Ser Glu Phe Thr Val Gln Ser Arg Tyr Tyr 180 185 190Leu Asn Phe Ser Ile Glu Asp Gln Val Gln Ile Asp Ser Thr Leu Met 195 200 205Thr Phe Ser Ala Leu Lys Ile Leu Leu Asn Asp Leu Lys Asp Tyr Leu 210 215 220Glu His Leu Asp Asn22519252PRTDermatophagoides farinae 19Glu Trp Arg Leu Val Trp Gln Asp Glu Phe Asn Gly Asn Gln Leu Asp1 5 10 15Leu Asn Gln Trp Ser Tyr Glu Val Gly Gly Asn Gly Trp Gly Asn Asn 20 25 30Glu Leu Glu Phe Tyr Thr Tyr Asn Arg Thr Glu Asn Ala Arg Ile Glu 35 40 45Asn Gly Asn Leu Val Ile Asp Val Arg Val Glu Asn Tyr Arg Glu Arg 50 55 60Gln Phe Thr Ser Ala Arg Leu His Thr Arg Gln Ala Trp Thr Tyr Gly65 70 75 80Arg Phe Glu Ala Arg Ala Arg Met Pro Tyr Gly His Asn Leu Trp Pro 85 90 95Ala Ile Trp Met Met Pro Gln Asp Ser Ile Tyr Gly Ile Trp Ala Ala 100 105 110Ser Gly Glu Ile Asp Ile Val Glu Tyr Arg Gly Asp Asn Pro Asp Arg 115 120 125Ile Glu Gly Thr Ala His Tyr Gly Gly Thr Trp Pro Asn His Ile Tyr 130 135 140Ser Gly Ser Gly Pro Arg Ser Phe Ser Val Asn Phe Ser Gln Asp Phe145 150 155 160His Thr Phe Ala Leu Glu Trp Asp His Lys Gln Leu Arg Trp Tyr Met 165 170 175Asp Asn Gln Gln Tyr Phe Thr Leu Asp Ile Asp Arg Met Leu Trp Ser 180 185 190Gly Lys Gly Val Asn Pro Tyr Thr Lys Asn Gly Gln Pro Phe Asp Gln 195 200 205Pro Phe His Trp Met Leu Asn Val Ala Val Gly Gly Asn Phe Phe Gly 210 215 220Pro Gly Pro Tyr Val Thr Pro Asp Gln Ala Arg Gln Trp Pro Lys His225 230 235 240Thr Leu Glu Ile Asp Tyr Val Arg Val Tyr Gln Gln 245 25020253PRTDermatophagoides pteronyssinus 20Asn Trp Gln Met Val Trp Gln Asp Glu Phe Asn Gly Gly His Leu Asp1 5 10 15Gln Asn His Trp Glu Phe Glu Thr Gly Gly Gly Gly Trp Gly Asn Asn 20 25 30Glu Leu Glu Phe Tyr Thr Ala Asn Arg Ser Gln Asn Val Arg Val Glu 35 40 45Asn Gly His Leu Val Ile Asp Val Arg Val Glu Ser Tyr Gly Gly Arg 50 55 60Asp Phe Thr Ser Gly Arg Ile His Ser Lys Gln Ala Trp Ala Tyr Gly65 70 75 80Lys Phe Glu Ala Arg Ala Arg Leu Pro Ser Gly His His Leu Trp Pro 85 90 95Ala Ile Trp Met Phe Pro Arg Asp Ser Lys Tyr Gly Pro Trp Ala Ala 100 105 110Ser Gly Glu Ile Asp Ile Met Glu Tyr Arg Gly Asp Val His Asp Lys 115 120 125Ile Glu Gly Thr Ile His Tyr Gly Gly Gln Trp Pro Asn Asn Ile Tyr 130 135 140Thr Gly Ser Gly Pro His His Phe Asn Val Asp Phe Ser Lys Asp Phe145 150 155 160His Asn Phe Ala Val Glu Trp Asp Thr Lys Glu Ile Arg Trp Tyr Met 165 170 175Asp Gly Asn Lys Tyr Phe Ser Val Asn Ile Asp Arg Asn Met Trp Ser 180 185 190Gly Lys Gly Asn Asn Pro Tyr Asn Lys Asn Gly Gln Pro Phe Asp Gln 195 200 205Pro Phe Arg Trp Ile Leu Asn Val Ala Val Gly Gly Asn Phe Phe Gly 210 215 220Pro Gly Pro Tyr Val Thr Pro Asp Gln Ala Arg His Trp Gln Lys His225 230 235 240Thr Met Glu Ile Asp Tyr Val Arg Val Tyr Gln Trp Arg 245 25021261PRTDermatophagoides farinae 21Met Ser Ser Ser Ser Gly Lys Lys Tyr Asp Phe Ser Gly Lys Val Ala1 5 10 15Leu Val Thr Gly Ser Ser Ser Gly Ile Gly Ala Ala Ile Ala Val Gln 20 25 30Phe Ala Gln Tyr Gly Ala Lys Leu Thr Ile Thr Gly Arg Asp Gly Ala 35 40 45Ala Leu Glu Ser Val Ala Lys Lys Ile Glu Ile Glu Ser Gly His Gln 50 55 60Pro Leu Gln Ile Val Gly Asp Leu Leu Asp Gln Ser Leu Pro Ala Lys65 70 75 80Leu Ile Asn Glu Thr Val Ser Lys Phe Gly Arg Leu Asp Phe Leu Val 85 90 95Asn Asn Ala Gly Gly Ser Thr Ala His Arg Glu Leu Asn Asp Glu Lys 100 105 110Leu Met Glu Ala Phe Asp Lys Val Phe Ala Leu Asn Val Arg Ala Val 115 120 125Leu Gln Leu Ser Gln Leu Ala Ala Ile His Leu Glu Lys Ser Lys Gly 130 135 140Asn Ile Ile Asn Ile Ser Ser Ile Val Ser Met Lys Pro Tyr Gly His145 150 155 160Val Tyr Ser Ser Ser Lys Ala Ala Leu Asp Met Ile Thr Lys Thr Leu 165 170 175Ala Lys Glu Leu Gly Leu Lys Gly Val Arg Val Asn Ser Ile Asn Pro 180 185 190Gly Pro Val Ala Thr Gly Phe Leu Arg Ser Val Gly Met Ser Ala Thr 195 200 205Ala Tyr Thr Asp Leu Ala Asp Thr Met Ile Asn His Thr Leu Leu Lys 210 215 220Phe Leu Ala Gln Pro Asp Glu Ile Ala Asn Leu Ala Ser Phe Leu Ala225 230 235 240Ser Asp Asp Ala Arg Asn Met Thr Gly Ser Ile Val Val Ser Asp Thr 245 250 255Gly Ser Leu Leu Val 26022262PRTDermatophagoides pteronyssinus 22Gln Ser Arg Asp Arg Asn Asn Lys Pro Tyr Arg Ile Val Cys Tyr Trp1 5 10 15Gly Thr Trp Ala Phe Tyr Arg Pro Gly Thr Gly Lys Phe Glu Ala Glu 20 25 30Asn Val Asn Pro Asn Leu Cys Thr His Leu Met Tyr Gly Phe Ala Lys 35 40 45Leu Gln Asn Asn Lys Ile Ala Leu Tyr Asp Pro Asp Leu Asp Asp Gly 50 55 60Asp Glu Asp Trp Asn Ser Gly Leu Asn Trp Gly His Gly Met Ile Arg65 70 75 80Arg Met Val Asn Leu Arg Thr Tyr Asn Pro His Leu Thr Thr Met Ile 85 90 95Ser Ile Gly Gly Trp Asn Glu Gly Ser Asp Lys Tyr Ser Met Met Val 100 105 110Arg Asp Pro Ser Ser Arg Lys Ile Phe Ile Gln Ser Val Leu Asp Leu 115 120 125Leu Ala Glu Phe Asp Leu Asp Gly Leu Asp Phe Asp Trp Glu Tyr Pro 130 135 140Ser Met Lys Ala Thr Gly Asp Asn Asp Arg Lys Pro Gly Arg Asp Glu145 150 155 160Asp Lys Glu Asp Phe Ile Thr Leu Leu Arg Glu Leu His Glu Ala Phe 165 170 175Gln Pro His Gly Tyr Leu Leu Ser Ser Ala Val Ser Ala Gly Lys Pro 180 185 190Thr Ile Asp Arg Ala Tyr Asn Ile Pro Glu Val Ser Lys Tyr Leu Asp 195 200 205Phe Ile Asn Leu Met Ser Tyr Asp Tyr His Gly Gly Trp Glu Ser His 210 215 220Thr Gly His Asn Ala Pro Leu Asn Ser Tyr Asp Asn Ala Asn Glu Leu225 230 235 240Asp Lys Glu Phe Thr Val Thr Tyr Ser Val Asp Tyr Trp Leu Ser His 245 250 255Gly Val Asp Ala Lys Asn 26023270PRTDermatophagoides farinae 23Ser Pro Ala Gln Arg Pro Ser Leu Arg Gly Val Thr Ile Arg Asn Ala1 5 10 15Pro Phe Leu Glu Glu Ile Asp Gly Lys Phe Lys Gly Phe Ile Pro Asp 20 25 30Leu Met Asp Ala Ile Ala Glu Lys Ala Gly Phe Asp Tyr Thr Leu Tyr 35 40 45Leu Ser Pro Asp Gly Arg Tyr Gly Asn Ala Asp Lys Glu Gly Asn Val 50 55 60Thr Gly Met Ile Gly Glu Val Tyr Asn Lys Lys Ala Asp Phe Ala Ala65 70 75 80Ala Asp Leu Thr Met Thr Glu Ala Arg Glu Asn Tyr Ile Thr Phe Thr 85 90 95Glu Pro Phe Met Ile Asn Gln Leu Ala Ala Leu Ile Arg Arg Glu Asp 100 105 110Ala Glu Gly Met Asn Thr Leu Glu Asp Leu Val Asn Ala Gly Lys Thr 115 120 125Gln Pro Asn His Lys Pro Ile Ile Leu Gly Thr Leu Arg Asn Gly Ala 130 135 140Thr Asn His Phe Leu Ser Lys Ser Asp Asp Pro Leu Ala Lys Lys Met145 150 155 160Tyr Glu Gln Ile Lys Ala Asn Asp Gln Ser Ala Thr Thr Ser Ile Ser 165 170 175Lys Gly Ile Glu Arg Val Asp Lys Gln Gly Gly Tyr Ala Phe Ile Met 180 185 190Glu Ser Ser Ser Ala Glu His Glu Ile Ala Asn Asn Cys Lys Leu Thr 195 200 205Met Leu Leu Asp Trp Arg Asn Leu Tyr Pro Arg Lys Tyr Ala Phe Ala 210 215 220Leu Pro Lys Asp Ser Gln Tyr Leu Gln His Phe Asn Asn Ala Ile Lys225 230 235 240Gln Leu Asn Thr Glu Asp Lys Ile Ala Glu Leu Arg Arg Lys Tyr Trp 245 250 255Ser Asn Asn Cys Ser Asn Thr Gln Thr Lys Asn Thr Gly Ala 260 265 27024271PRTDermatophagoides pteronyssinus 24Asp Pro Val Gln Gln Arg Pro Thr Leu Arg Gly Val Thr Val Arg Val1 5 10 15Gly Pro Phe Val Lys Glu Asn Asn Gly Lys Phe Glu Gly Phe Ile Pro 20 25 30Asp Leu Val Gln Ala Ile Ser Glu Lys Val Gly Phe Asp Tyr Thr Leu 35 40 45Tyr Leu Ser Pro Asp Gly Arg Tyr Gly Asn Val Ile Ser Asp Gly Asn 50 55 60Val Thr Gly Met Ile Gly Glu Val Tyr Asn Lys Lys Ala Asp Phe Ala65 70 75 80Ala Ala Asp Leu Thr Met Thr Glu Ala Arg Glu Asn Tyr Ile Thr Phe 85 90 95Thr Glu Pro Phe Met Ile Asn Gln Leu Ala Ala Leu Ile Arg Arg Glu 100 105 110Asp Ala Glu Gly Leu Asn Thr Leu Glu Asp Leu Ala Lys Ala Gln Glu 115 120 125Thr Phe Pro Lys Arg Lys Arg Ile Val Leu Gly Thr Leu Arg Asn Gly 130 135 140Ala Thr Asn Tyr Phe Leu Ser Lys Ser Asp Asp Pro Leu Ala Lys Lys145 150 155 160Ile Tyr Glu Gln Ile Lys Ala Asp Asp Gln Ser Val Val Lys Ser Ile 165 170 175Ser Glu Gly Val Glu Arg Val Asp Lys Gln Gly Gly Tyr Ala Phe Ile 180 185 190Met Glu Ser Ala Ser Ala Glu His Glu Ile Ala Asn Asn Cys Lys Leu 195 200 205Thr Met Leu Leu Asp Trp Arg Asn Leu Phe Pro Arg Lys Tyr Ala Phe 210 215 220Ala Leu Pro Lys Asp Ser Pro Tyr Leu Glu His Phe Asn Asn Ala Ile225 230 235 240Lys Gln Leu Asn Ser Glu Gly Lys Ile Ala Glu Leu Arg Arg Lys Tyr 245 250 255Trp Ala Asn Asn Cys Ala Glu Asn Lys Thr Lys Asp Asp Lys Asn 260 265 27025275PRTDermatophagoides pteronyssinus 25Met Ser Ser Ser Ser Gly Lys Lys Tyr Asp Phe Ser Gly Lys Val Ala1 5 10 15Leu Val Thr Gly Ser Ser Ser Gly Ile Gly Ala Ala Ile Ala Leu Gln 20 25 30Phe Ala Gln Tyr Gly Ala Gln Val Thr Ile Thr Gly Arg Asp Ala Ala 35 40 45Ala Leu Glu Ser Val Ala Lys Arg Ile Glu Ala Glu Ser Gly His Gln 50 55

60Pro Leu Gln Ile Val Gly Asn Leu Leu Asp Gln Ser Leu Pro Ala Lys65 70 75 80Leu Ile Asp Gly Thr Ile Ser Lys Tyr Gly Arg Leu Asp Phe Leu Val 85 90 95Asn Asn Ala Gly Phe Ser Thr Gln His Arg Asp Ile His Asp Glu Lys 100 105 110Leu Met Glu Ala Phe Asp Gln Val Tyr Gly Leu Asn Val Arg Ala Val 115 120 125Val Gln Leu Ser Gln Leu Ala Ala Thr His Leu Glu Lys Ser Lys Gly 130 135 140Asn Ile Ile Asn Ile Ser Ser Asn Leu Ser Met Met Pro Val His Ile145 150 155 160Ile Tyr Ser Ser Ser Lys Ala Ala Leu Asp Met Ile Thr Lys Thr Met 165 170 175Ala Met Glu Phe Gly Lys Lys Gly Val Arg Val Asn Ser Ile Asn Pro 180 185 190Gly Pro Val Ala Thr Gln Phe Met Arg Ser Leu Gly Met Pro Val Thr 195 200 205Phe Leu Lys Glu Asn Glu Glu Phe Val Lys Glu Leu Thr Leu Leu Lys 210 215 220Phe Val Ala Gln Pro Val Glu Ile Ala Asn Leu Ala Ser Phe Leu Ala225 230 235 240Ser Asp Asp Ala Arg Asn Met Thr Gly Ser Ile Val Val Asn Asp Thr 245 250 255Gly Ser Leu Leu Ala Pro Arg Val Asp Phe Lys Lys Leu Asp Glu Ile 260 265 270Lys Lys Lys 27526310PRTDermatophagoides farinae 26Ser Pro Thr Ser Ile Arg Thr Phe Glu Glu Phe Lys Arg Gln Phe Asn1 5 10 15Lys Gln Tyr Gln Ser Ile Glu His Glu Glu Ile Ala Arg Lys Asn Phe 20 25 30Gln Glu Thr Leu Arg Tyr Val Gln Ala Asn Gln Asp Lys Ala Val Ile 35 40 45Asn Glu Tyr Ala Asp Leu Ser Ala Glu Glu Phe Ala Asp Gly Tyr Leu 50 55 60Met Asn Val Gln Asp Val Gln Asp Leu Glu Ala Glu Met Asp Ala His65 70 75 80Lys Glu Tyr Phe Asp Asp Pro Asp Cys Lys Leu His Gly Asp Phe Asn 85 90 95Pro Pro Lys Glu Phe Asp Leu Arg Pro His Leu Thr Pro Ile Lys Lys 100 105 110Gln Ile Lys Asn Cys Gly Cys Cys Trp Ala Leu Ser Thr Ile Ser Cys 115 120 125Val Glu Thr Ala Tyr Leu Ala Gln Lys Asn Val Ser Leu Gln Leu Ser 130 135 140Thr Gln Glu Leu Val Asn Cys Ala Lys Glu His Gly Cys Lys Lys Gly145 150 155 160Thr Val Leu Asp Gly Ile Glu Tyr Ile Met Ala Asn Gly Thr Thr Thr 165 170 175Glu Glu Ala Cys Pro Phe Ile Ser Glu Glu Ser Thr Cys Asp Gln Ser 180 185 190Lys Lys Pro Arg Tyr Glu Ile Ser Asn Trp Cys Tyr Phe Lys Pro Val 195 200 205Glu Asp Asp Ile Arg Lys Asn Leu Val Leu Arg Arg Thr Ser Val Ser 210 215 220Val Ser Met Asn Ile Glu Asn Leu Lys Ala Phe Val His Tyr Asp Gly225 230 235 240Ser Phe Val Ile Arg Glu Asn Ser Phe Pro Ser Ile Gly Asn Lys Ser 245 250 255Tyr His Ala Val Asn Ile Val Gly Phe Gly Thr Lys Asp Asp Ile Asp 260 265 270His Trp Ile Val Arg Asn Ser Trp Gly Glu Lys Trp Gly Asp Lys Gly 275 280 285Tyr Phe Tyr Val Glu Arg Asp Ile Asn Leu Trp Gly Ile Lys Asp Trp 290 295 300Ala Phe Thr Thr Ile Val305 31027321PRTDermatophagoides pteronyssinus 27Ser Pro Thr Gly Trp Asn Ile Arg Thr Phe Glu Gln Phe Lys Ile Gln1 5 10 15Phe Asn Lys His Tyr Asp Ser Ile Glu Gln Glu Glu His Ala Arg Glu 20 25 30Asn Phe Leu Glu Thr Leu Lys Tyr Val Asp Ala Asn Pro Asp Lys Ala 35 40 45Val Ile Asn Glu Phe Ala Asp Leu Ser Ala Glu Glu Phe Ala Asp Gly 50 55 60Tyr Leu Met Ser Glu Glu Ser Met Gln Asp Ser Glu Gln Gln Leu Lys65 70 75 80Leu Leu Arg Ala Gly Tyr Asp Tyr His Asp Asp Pro Glu Cys Leu Phe 85 90 95Asp Glu Asn Leu Glu Ala Pro Lys Gln Val Asp Leu Arg Pro Asp Leu 100 105 110Ser Pro Ile Met Arg Gln Thr Leu His Cys Gly Cys Cys Trp Ala Ile 115 120 125Ser Pro Ile Ser Ser Ala Glu Ser Ala Tyr Lys Ala Arg Tyr Asn Val 130 135 140Ser Ile Gln Leu Ser Val Gln Glu Leu Val Asn Cys Ala Val Glu His145 150 155 160Gly Cys Glu Ile Gly Lys Thr Ala Ile Ala Phe Asn Tyr Leu Val Thr 165 170 175Asn Gly Thr Thr Thr Gln Lys Ala Tyr Pro Tyr Thr Ala Lys Glu Gly 180 185 190Ala Cys Asn Pro Pro Glu Lys Pro Arg Tyr Thr Leu Glu Asn Trp Cys 195 200 205Ala Tyr Ile Asp Pro Ser Ile Lys Asn Lys Asn Lys Pro Asp Leu Arg 210 215 220Lys Val Leu Ala Gln Lys Arg Thr Ser Ile Thr Val Gln Ile Ser Ile225 230 235 240Lys Asn Val Lys Ala Phe Ala His His Asn Gly Ser Phe Ile Ile Arg 245 250 255Glu Asn Ser Phe Pro Asp Glu Gly Lys Pro Ser Gly His Ala Ile Asn 260 265 270Ile Val Gly Tyr Gly Thr Lys Asp Gly Val Asp Tyr Trp Ile Val Arg 275 280 285Asn Ser Trp Ser Thr Gly Trp Gly Asp Lys Gly Tyr Phe Tyr Val Glu 290 295 300Arg Gly Val Asn Trp Trp Gly Ile Glu Glu Tyr Ala Phe Ile Ala Thr305 310 315 320Phe28332PRTDermatophagoides farinae 28Met Val Lys Ile Gly Ile Asn Gly Phe Gly Arg Ile Gly Arg Leu Val1 5 10 15Leu Arg Ala Ala Val Lys Lys Gly Val Glu Val Val Ala Val Asn Asp 20 25 30Pro Phe Leu Asp Val Lys Tyr Met Val Tyr Met Phe Lys Phe Asp Ser 35 40 45Thr His Gly Arg Tyr Gln Gly Glu Val Lys Glu Glu Gly Gly Leu Leu 50 55 60Val Val Asp Gly Gln Lys Ile Gln Val Phe Gln Glu Arg Asn Pro Ala65 70 75 80Asp Ile Pro Trp Gly Lys Val Gly Ala Asp Tyr Val Val Glu Ser Thr 85 90 95Gly Val Phe Thr Thr Ile Glu Lys Ala Lys Ala His Leu Ala Gly Gly 100 105 110Ala Lys Lys Val Val Ile Ser Ala Pro Ser Ala Asp Ala Pro Met Tyr 115 120 125Val Met Gly Val Asn His Asp Lys Tyr Asp Pro Ser Gln Gln Ile Ile 130 135 140Ser Asn Ala Ser Cys Thr Thr Asn Cys Leu Ala Pro Leu Ala Lys Val145 150 155 160Ile Asn Asp Lys Phe Gly Ile Glu Asn Gly Leu Met Thr Thr Val His 165 170 175Ala Val Thr Ala Thr Gln Lys Thr Val Asp Gly Pro Ser Gly Lys Met 180 185 190Trp Arg Asp Gly Arg Gly Ala Gly Gln Asn Ile Ile Pro Ala Ser Thr 195 200 205Gly Ala Ala Lys Ala Val Gly Lys Val Ile Pro Glu Leu Asn Gly Lys 210 215 220Leu Thr Gly Met Ala Leu Arg Val Pro Val Pro Asp Val Ser Val Val225 230 235 240Asp Leu Thr Val Thr Leu Lys Asn Pro Ala Ser Tyr Asp Glu Ile Lys 245 250 255Ala Ala Ile Lys Ala Ala Ala Glu Ser Asp His Trp Lys Gly Ile Leu 260 265 270Glu Tyr Thr Asp Glu Glu Val Val Ser Ser Asp Phe Ile Ser Asp Thr 275 280 285His Ser Ser Ile Phe Asp Ala Lys Ala Gly Ile Ala Leu Thr Pro Thr 290 295 300Phe Val Lys Leu Ile Ala Trp Tyr Asp Asn Glu Phe Gly Tyr Ser Asn305 310 315 320Arg Val Ile Asp Leu Ile Lys Tyr Val Ala Ser Lys 325 33029332PRTDermatophagoides pteronyssinus 29Met Val Lys Ile Gly Ile Asn Gly Phe Gly Arg Ile Gly Arg Leu Val1 5 10 15Leu Arg Ala Ala Ile Lys Lys Gly Val Glu Val Ala Ala Ile Asn Asp 20 25 30Pro Phe Leu Asp Val Lys Tyr Met Val Tyr Met Phe Lys Phe Asp Ser 35 40 45Thr His Gly Arg Tyr Gln Gly Glu Val Lys Glu Glu Gly Gly Leu Leu 50 55 60Val Val Asp Gly Gln Lys Ile Gln Val Phe Gln Glu Arg Asn Pro Ala65 70 75 80Glu Ile Pro Trp Gly Lys Val Gly Ala Asp Tyr Val Val Glu Ser Thr 85 90 95Gly Val Phe Thr Thr Ile Glu Lys Ala Lys Ala His Leu Ala Gly Gly 100 105 110Ala Lys Lys Val Ile Ile Ser Ala Pro Ser Ala Asp Ala Pro Met Tyr 115 120 125Val Met Gly Val Asn His Asp Lys Tyr Asp Pro Lys Gln Gln Ile Ile 130 135 140Ser Asn Ala Ser Cys Thr Thr Asn Cys Leu Ala Pro Leu Ala Lys Val145 150 155 160Ile Asn Asp Lys Phe Gly Ile Glu Asn Gly Leu Met Thr Thr Val His 165 170 175Ala Ile Thr Ala Thr Gln Lys Thr Val Asp Gly Pro Ser Gly Lys Leu 180 185 190Trp Arg Asp Gly Arg Gly Ala Gly Gln Asn Ile Ile Pro Ala Ser Thr 195 200 205Gly Ala Ala Lys Ala Val Gly Lys Val Ile Pro Glu Leu Asn Gly Lys 210 215 220Leu Thr Gly Met Ala Leu Arg Val Pro Val Pro Asp Val Ser Val Val225 230 235 240Asp Leu Thr Val Thr Leu Lys Asn Pro Ala Ser Tyr Asp Glu Ile Lys 245 250 255Ala Ala Val Lys Ala Ala Ala Glu Ser Asp His Trp Lys Gly Ile Leu 260 265 270Glu Tyr Thr Asp Glu Glu Val Val Ser Ser Asp Phe Ile Ser Asp Thr 275 280 285His Ser Ser Ile Phe Asp Ala Lys Ala Gly Ile Ala Leu Thr Pro Thr 290 295 300Phe Val Lys Leu Ile Ala Trp Tyr Asp Asn Glu Phe Gly Tyr Ser Asn305 310 315 320Arg Val Val Asp Leu Ile Lys Tyr Val Ala Ser Lys 325 33030361PRTDermatophagoides farinae 30Met Ala Lys Phe Asn Tyr Leu Pro Val Asp Val Gln Glu Glu Leu Arg1 5 10 15Asn Thr Ala Asn Ala Ile Val Ser Val Gly Lys Gly Ile Leu Ala Ala 20 25 30Asp Glu Ser Thr Gly Thr Ile Gly Lys Arg Phe Ala Asp Ile Asn Val 35 40 45Glu Asn Val Glu Pro Asn Arg Arg Ala Tyr Arg Gln Leu Leu Phe Tyr 50 55 60Ser Glu Asn Ile Glu Gln Tyr Ile Ser Gly Val Ile Leu Phe Asp Glu65 70 75 80Thr Val Tyr Gln Lys Asp Asp Asn Asn Thr Pro Phe Pro Glu Leu Leu 85 90 95Lys Lys Lys Gly Ile Ile Pro Gly Ile Lys Val Asp Thr Gly Val Val 100 105 110Thr Leu Gln Gly Thr Asn Gly Glu Ser Thr Thr Gln Gly Leu Asp Asn 115 120 125Leu Thr Lys Arg Cys Gln Glu Tyr Tyr Asn His Gly Cys Arg Phe Ala 130 135 140Lys Trp Arg Cys Val Leu Lys Ile Gly Lys Asp Glu Pro Ser Ala Leu145 150 155 160Ala Ile Leu Glu Asn Ala Asn Val Leu Ala Arg Tyr Ala Ser Cys Cys 165 170 175Gln Gln Ala Arg Ile Val Pro Ile Val Glu Pro Glu Ile Leu Pro Asp 180 185 190Gly Asp His Asp Leu Glu Arg Cys Gln Lys Val Thr Glu Thr Val Leu 195 200 205Ala Ala Val Tyr Lys Ala Leu Asn Asp His His Val Tyr Leu Glu Gly 210 215 220Ser Leu Leu Lys Pro Asn Met Val Thr Pro Gly Gln Ser Cys Pro Gln225 230 235 240Lys Ala Ser Pro Gln Asp Ile Ala Arg Ala Thr Val Thr Ala Leu Gln 245 250 255Arg Thr Val Pro Ala Ala Val Pro Gly Val Val Phe Leu Ser Gly Gly 260 265 270Gln Ser Glu Glu Glu Ala Ser Val Asn Leu Asn Ala Ile Asn Gln Tyr 275 280 285Gln Gly Lys Lys Pro Trp Ala Leu Ser Phe Ser Tyr Gly Arg Ala Leu 290 295 300Gln Ala Ser Ala Leu Arg Ala Trp Gln Gly Lys Pro Glu Asn Ile Ser305 310 315 320Ala Gly Gln Lys Glu Phe Leu Gln Arg Ala Lys Ala Asn Ser Leu Ser 325 330 335Ala Gln Gly Gln Tyr Thr Gly Gly Val Val Gly Ala Ala Ala Asp Gln 340 345 350Asp Leu Phe Ile Lys Asp His Gln Tyr 355 36031362PRTDermatophagoides pteronyssinus 31Met Ala Lys Phe Asn Tyr Leu Pro Val Asp Val Gln Glu Glu Leu Arg1 5 10 15Asn Thr Ala Asn Ala Ile Val Ser Val Gly Lys Gly Ile Leu Ala Ala 20 25 30Asp Glu Ser Thr Gly Thr Ile Gly Lys Arg Phe Ala Asp Ile Asn Val 35 40 45Glu Asn Val Glu Gln Asn Arg Gln Ala Tyr Arg Gln Leu Leu Phe Tyr 50 55 60Ser Glu Gly Ile Glu Gln Tyr Ile Ser Gly Val Ile Leu Phe Asp Glu65 70 75 80Thr Val Tyr Gln Lys Asp Asp Lys Gly Val Pro Phe Pro Glu Leu Leu 85 90 95Lys Lys Lys Gly Ile Ile Pro Gly Ile Lys Val Asp Thr Gly Val Val 100 105 110Thr Leu Gln Gly Thr Asn Gly Glu Ser Thr Thr Gln Gly Leu Asp Asn 115 120 125Leu Thr Lys Arg Cys Gln Glu Tyr Tyr Asn Gln Gly Cys Arg Phe Ala 130 135 140Lys Trp Arg Cys Val Leu Lys Ile Gly Gln Asp Glu Pro Ser Ser Leu145 150 155 160Ala Ile Val Glu Asn Ala Asn Val Leu Ala Arg Tyr Ala Ser Cys Cys 165 170 175Gln Gln Ala Arg Ile Val Pro Ile Val Glu Pro Glu Ile Leu Pro Asp 180 185 190Gly Asp His Asn Leu Glu Arg Cys Gln Lys Val Thr Glu Thr Val Leu 195 200 205Ala Ala Val Tyr Lys Ala Leu Asn Asp His His Val Tyr Leu Glu Gly 210 215 220Thr Leu Leu Lys Pro Asn Met Val Thr Pro Gly Gln Ser Cys Pro Gln225 230 235 240Lys Ala Ser Pro Gln Glu Val Ala Gln Ala Thr Val Thr Ala Leu Gln 245 250 255Arg Thr Val Pro Ala Ala Val Pro Gly Ile Val Phe Leu Ser Gly Gly 260 265 270Gln Ser Glu Glu Glu Ala Ser Val Asn Leu Asn Ala Ile Asn Gln Tyr 275 280 285Gln Gly Lys Lys Pro Trp Ala Leu Ser Phe Ser Tyr Gly Arg Ala Leu 290 295 300Gln Ala Ser Ala Leu Arg Ala Trp Gln Gly Lys Pro Glu Asn Ile Gly305 310 315 320Ala Gly Gln Lys Glu Leu Leu Gln Arg Ala Lys Ala Asn Val Leu Ala 325 330 335His Lys Gly Gln Tyr Val Ala Gly Ser Ile Pro Ser Leu Ala Ser Ala 340 345 350Lys Ser Asn Phe Val Ala Gln His Lys Tyr 355 36032429PRTDermatophagoides farinae 32Ile Glu Gln Val His Ile Ser Leu Gly Thr Asn Ala Thr Glu Met Ile1 5 10 15Val Thr Trp Thr Glu Pro Gln Lys His Thr Asp Ile Asp Ile Asp Ala 20 25 30Val Val Tyr Tyr Gly Arg Ala Ser Ser Ser Phe Asp Gln Ala Ala Ile 35 40 45Ala Lys Ser Glu His Phe Lys Asp Asp Glu Thr Lys Tyr Thr Thr Phe 50 55 60Arg Ala Leu Leu Thr Gly Leu Glu Ser Asp Thr Arg Tyr His Tyr Lys65 70 75 80Ile Gln Leu Asp Asp Lys Glu Ser Ser Ile Phe Ala Phe Lys Thr Leu 85 90 95Lys Leu Asp Glu Asn Trp Leu Pro Arg Phe Ala Ile Tyr Gly Asp Leu 100 105 110Gly Tyr Val Asn Glu Gln Ser Leu Pro Tyr Leu Lys Lys Asp Val Glu 115 120 125Lys Asn Met Phe Asp Val Ile Phe His Ile Gly Asp Ile Ala Tyr Asp 130 135 140Leu Gln Asp Glu Asn Gly Glu Val Gly Asn Asn Phe Met Arg Ser Ile145 150 155 160Glu Ser Ile Ala Ser Lys Ile Pro Tyr Met Thr Cys Pro Gly Asn His 165 170 175Glu Arg His Ser Asn Phe Ser His Tyr Asp Ser Arg Phe Ser Met Ile 180 185 190Gly Asp Arg Ser Gln Pro Asn His Gln Asp Ser Leu Asp Lys Arg Ile 195 200 205Asn Asn His Phe His Ser Met Glu Ile Gly Pro Ala Thr Ile Ile Met 210

215 220Phe Ser Thr Glu Tyr Tyr Tyr Tyr Thr Tyr Tyr Gly Trp Glu Gln Ile225 230 235 240Glu Arg Gln Tyr Arg Phe Leu Glu Lys Glu Leu Ile Arg Ala Asn Glu 245 250 255Asn Arg Asn Lys Arg Pro Trp Ile Ile Ala Met Gly His Arg Pro Leu 260 265 270Tyr Cys Leu Lys Met Gly Asp Ser Ser Cys Asp His Gln Thr Met Glu 275 280 285Arg Pro Glu Ile Arg Gln Gly Ile Arg Met His Asp Gln Gly Glu Arg 290 295 300Gln Tyr Gly Leu Glu Asp Leu Phe His Lys Tyr Gly Val Asp Ile Gln305 310 315 320Phe Tyr Gly His Glu His Phe Tyr Ala Arg Met Phe Pro Ile Tyr Lys 325 330 335Tyr Gln Met Tyr Lys Gly Lys Gln Ser Asp Asn Pro Tyr Asp His Ala 340 345 350Asp Gly Pro Ile His Ile Thr Thr Gly Ser Ala Gly Asn Lys Glu Ile 355 360 365His Pro Leu Phe Asn His Leu Lys Glu Trp Val Ala His His Phe Tyr 370 375 380Asp Tyr Gly Tyr Thr Arg Leu Ile Phe Glu Asn Gln Tyr Arg Ile Arg385 390 395 400Leu Gln Gln Val Ser Asp Asp Gln His Gly Lys Val Leu Asp Glu Ile 405 410 415Glu Ile Ile Lys Ser Ser Pro Gln Pro His Trp Met Pro 420 42533434PRTDermatophagoides pteronyssinus 33Ile Glu Gln Val His Ile Ala Leu Gly Ser Asn Glu Thr Glu Ile Ile1 5 10 15Val Thr Trp Thr Glu Pro His Lys His Asp Asp Lys Thr Ser Asp Ala 20 25 30Val Val Tyr Tyr Gly Gln Ala Lys Ser Ser Phe Asp Gln Lys Val Lys 35 40 45Ala Ile Ser Glu Tyr Phe Lys Asp Asp Lys Thr Lys Tyr Thr Thr Tyr 50 55 60Arg Ala Leu Leu Thr Gly Leu Leu Pro Gly Thr Glu Tyr His Tyr Arg65 70 75 80Ile Gln Met Asp Asp Leu Glu Ser Ser Ile Phe Glu Phe Lys Thr Leu 85 90 95Lys Thr Gly Glu Glu Asn Trp Leu Pro Arg Phe Ala Ile Tyr Gly Asp 100 105 110Leu Gly Tyr Val Asn Glu Gln Ser Leu Pro Tyr Leu Lys Lys Asp Val 115 120 125Glu Gln Asn Leu Phe Asp Val Ile Phe His Ile Gly Asp Phe Ala Tyr 130 135 140Asp Leu Asn Asp Glu His Gly Lys Val Gly His His Phe Met Arg Ser145 150 155 160Ile Glu Pro Val Ala Ser Lys Val Ala Tyr Met Thr Cys Pro Gly Asn 165 170 175His Glu Arg His Asp Asn Phe Ser His Tyr Asp Ser Arg Phe Ser Met 180 185 190Ile Gly Asp Arg Ser Gln Pro Ile His Ser Asp Lys Leu Asn Lys Arg 195 200 205Leu Asn Asn His Phe His Ser Met Thr Ile Gly Pro Ala Thr Ile Ile 210 215 220Leu Phe Ser Thr Glu Tyr Tyr Tyr Tyr Thr Lys Tyr Gly Trp Gln Gln225 230 235 240Ile Glu His Gln Tyr Arg Trp Leu Glu Gln Glu Leu Lys Arg Ala Asn 245 250 255Glu Asn Arg Gln Lys His Pro Trp Ile Ile Val Met Gly His Arg Pro 260 265 270Leu Tyr Cys Leu Lys Met Gly Asp Asp Ser Cys Asp His Gln Thr Met 275 280 285Glu Arg Lys Glu Ile Arg Gln Gly Ile Arg Met His Asp Glu Gly Glu 290 295 300Arg Gln Tyr Gly Leu Glu Asp Leu Phe Phe Lys Tyr Gly Val Asp Ile305 310 315 320Gln Phe Tyr Gly His Glu His Phe Tyr Ala Arg Leu Phe Pro Ile Tyr 325 330 335Lys Tyr Lys Met Tyr Asn Gly Thr Lys Ser Lys Asn Pro Tyr Asp His 340 345 350Pro Gly Ala Pro Ile His Ile Thr Thr Gly Ser Ala Gly Asn Lys Glu 355 360 365Leu His Pro Glu Phe Asn His Leu Asn Asp Trp Val Ala Glu His Phe 370 375 380Tyr Asp Tyr Gly Tyr Thr Arg Leu Met Phe Glu Asp Lys Tyr Arg Ile385 390 395 400Arg Leu Gln Gln Ile Ser Asp Asp Gln His Gly Lys Val Leu Asp Glu 405 410 415Ile Glu Ile Val Lys Ser Ser Pro Gln Pro His Trp Met Asn Val Glu 420 425 430His His34462PRTDermatophagoides farinae 34Asp Ser Asn Ser Asp Thr Thr Phe Ile Phe Asn Gly Asp Gly Cys Glu1 5 10 15Gln Asn His Leu Phe Gln Thr Arg Tyr Arg Pro Gln Ile Gln Gln Leu 20 25 30Ala Ser Asp Val Gln Arg Ile Ile Asp His Val Met Ser Val Asn Glu 35 40 45Ser Gly Arg Thr Tyr Arg Gln Leu Ala Glu Phe Val Asp Arg Phe Gly 50 55 60Ser Arg Leu Thr Gly Thr Lys Asn Leu Glu Asp Ser Ile Asp Tyr Met65 70 75 80Ile Asp Leu Leu Arg Gln Glu Gly His Asp Asn Val His Gly Glu Ser 85 90 95Val Gln Val Pro Arg Trp Thr Arg Gly Asn Glu Trp Ala Arg Met Ile 100 105 110Lys Pro Arg Glu Lys Lys Leu Asn Ile Leu Gly Leu Gly Tyr Ser Glu 115 120 125Gly Thr Asn Gly Gln Thr Ile Glu Ala Pro Ile Val Val Val Arg Asn 130 135 140Phe Thr Glu Leu Glu Gln Lys Ser Arg Leu Ile Pro Gly Lys Ile Val145 150 155 160Val Tyr Asn Phe His Tyr Glu Ser Tyr Gly Lys Gln Ala Ile Tyr Arg 165 170 175His Ser Gly Ala Ser Arg Ala Ala Glu Phe Gly Ala Val Ala Ala Met 180 185 190Ile Arg Ser Leu Thr Pro Phe Ser Ile Asp Ser Pro His Thr Gly Met 195 200 205Gln Thr Tyr Asp Val Asn Val Thr Arg Ile Pro Ala Ile Ser Ile Thr 210 215 220Ala Glu Asp Ala Asp Leu Phe Gln Arg Phe Ser Asp Arg Asn Glu Glu225 230 235 240Val Ile Val Gln Ile Tyr Ser Glu Asn Arg Asn Glu Lys Glu Gln Gly 245 250 255Ile Ser Arg Asn Thr Val Ser Asp Ile Arg Gly Glu Gln Tyr Pro Asp 260 265 270Glu Ile Val Leu Val Ser Gly His Ile Asp Ser Trp Asp Val Gly Gln 275 280 285Gly Ala Leu Asp Asp Gly Ala Gly Ser Phe Ile Ser Trp Arg Ala Leu 290 295 300Ser Val Ile Lys Gln Leu Gly Leu Arg Pro Lys Arg Thr Met Arg Ser305 310 315 320Ile Leu Trp Thr Gly Glu Glu Phe Gly Leu Ile Gly Val Tyr Asp Tyr 325 330 335Val Lys Lys His Gln Asn Glu Leu Lys Asn Tyr Val Leu Ala Met Glu 340 345 350Ser Asp Ile Gly Thr Phe Thr Pro Lys Gly Ile Thr Phe Ser Gly Arg 355 360 365Asn Ser Thr Ser Gln Cys Thr Leu Trp Glu Ile Leu Gln Leu Met His 370 375 380Pro Ile Asn Ala Thr Thr Leu Thr Ile Ser Thr Glu Gly Ser Asp Val385 390 395 400Gln Ala Phe Tyr Glu Asn Gly Val Pro Ile Ser Ser Leu Asp Thr Ala 405 410 415Asn Asp Lys Tyr Phe Tyr Phe His His Thr Gln Gly Asp Thr Met Thr 420 425 430Val Glu Gln Ser Asp Asp Leu Asp Lys Cys Gln Ala Leu Trp Thr Ser 435 440 445Ile Ser Tyr Ala Leu Ala Met Leu Asp Asp Arg Leu Pro Arg 450 455 46035462PRTDermatophagoides pteronyssinus 35Asp Ser Asn Pro Gly Glu Thr Ser Ile Phe Asn Gly Glu Gly Cys Ala1 5 10 15Asn Asp Gln Leu Phe Gln Thr Arg Ile Arg Pro Gln Ile Gln Gln Leu 20 25 30Ala Ser Asn Val Gln Arg Ile Ile Asp His Val Met Ser Ala Asn Glu 35 40 45Ser Gly Arg Thr Tyr Arg Gln Leu Ala Glu Phe Val Asp Arg Phe Gly 50 55 60Ser Arg Leu Thr Gly Thr Lys Asn Leu Glu Asp Ser Ile Asp Tyr Met65 70 75 80Ile Asp Leu Leu Lys Gln Glu Gly His Asp Asn Val His Gly Glu Pro 85 90 95Val Gln Val Pro Lys Trp Thr Arg Gly Asn Glu Trp Ala Arg Met Ile 100 105 110Lys Pro Arg Asp Lys Lys Leu Asn Ile Leu Gly Leu Gly Tyr Ser Glu 115 120 125Gly Thr Asn Gly Gln Thr Ile Glu Ala Pro Ile Val Val Val Arg Asn 130 135 140Phe Thr Glu Leu Glu Gln Lys Ala Gly Leu Ile Pro Gly Lys Ile Val145 150 155 160Val Tyr Asn Phe Lys Tyr Glu Ser Tyr Gly Lys Gln Ala Ile Tyr Arg 165 170 175His Ser Gly Ala Ser Arg Ala Ala Lys Phe Gly Ala Val Ala Ala Met 180 185 190Ile Arg Ser Leu Thr Pro Phe Ser Ile Asp Ser Pro His Thr Gly Met 195 200 205Gln Ser Tyr Asp Val Asn Val Thr Lys Ile Pro Ala Ile Ser Ile Thr 210 215 220Thr Glu Asp Ala Asp Leu Phe Gln Arg Phe Ser Asp Arg Asn Glu Glu225 230 235 240Val Ile Val Gln Ile Tyr Ser Glu Asn His Asn Glu Lys Asp Lys Gly 245 250 255Ile Ser Arg Asn Thr Val Ser Asp Val Arg Gly Glu Lys Tyr Pro Asn 260 265 270Glu Ile Val Leu Val Ser Gly His Ile Asp Ser Trp Asp Val Gly Gln 275 280 285Gly Ala Ser Asp Asp Gly Ala Gly Ala Phe Ile Ser Trp Arg Ala Leu 290 295 300Ser Val Ile Lys Lys Leu Gly Leu Arg Pro Lys Arg Thr Leu Arg Ser305 310 315 320Val Leu Trp Thr Gly Glu Glu Phe Gly Leu Ile Gly Val Tyr Asp Tyr 325 330 335Ile Lys Lys His Arg Asn Glu Leu Lys Asp Tyr Val Ile Ala Met Glu 340 345 350Ser Asp Ile Gly Thr Phe Thr Pro Arg Gly Ile Thr Tyr Ser Gly Lys 355 360 365Asn Ser Thr Ser Gln Cys Thr Leu Trp Glu Ile Leu Gln Leu Met His 370 375 380Pro Ile Asn Ala Thr Thr Leu Thr Ile Ser Thr Glu Gly Ser Asp Val385 390 395 400Gln Ala Phe Tyr Glu Asn Gly Val Pro Ile Ser Ser Leu Asp Thr Ala 405 410 415Asn Asp Lys Tyr Phe Tyr Phe His His Thr Gln Gly Asp Thr Met Thr 420 425 430Val Glu Gln Pro Asp Asp Leu Asp Lys Cys Gln Ala Leu Trp Thr Ser 435 440 445Val Ser Tyr Ala Leu Ala Met Leu Asp Asp Arg Leu Ser Arg 450 455 46036463PRTDermatophagoides farinae 36Asp Thr Pro Ala Asn Cys Thr Tyr Glu Asp Ile Lys Gly Leu Trp Leu1 5 10 15Phe Glu Glu Ser Thr Pro Ile Asn Asp Arg Thr Glu Lys Cys Asp Asn 20 25 30Gly Arg Arg Glu Tyr Thr Lys Lys Ile Tyr Val Arg Leu Asp Phe Pro 35 40 45Asn Thr Ala Val Asp Lys Phe Gly Asn Val Gly Thr Trp Thr Leu Ile 50 55 60Tyr Asn Gln Gly Phe Glu Val Ile Ile Asn Tyr Arg Lys Tyr Phe Ala65 70 75 80Phe Ser Ala Tyr Glu Arg Lys Ser Asn Ser Lys Val Ile Ser Tyr Cys 85 90 95His Lys Thr Ile Pro Gly Trp Ser His Asp Leu Leu Gly Asn Asn Trp 100 105 110Ala Cys Tyr Ile Gly His Lys Val Asn Asp Trp Asn Ser Ser Pro Leu 115 120 125Gln Lys Ile Gly Ser Glu Gln Phe Pro Ile Lys Glu His Ile Glu Gln 130 135 140Pro Leu Tyr Leu Lys Asn Ile Asp Leu Ser His Ala Leu Ser Gln Asn145 150 155 160His Val Asp Gln Ile Asn Ser Lys Gln Lys Ser Trp Lys Ala Thr Val 165 170 175Tyr Pro Glu Met Gln Ser Lys Thr Val Glu His Leu Ile Lys Met Ala 180 185 190Gly Gly Glu Lys Ser Arg Ile Met Ser Arg Pro Lys Pro Ile Arg Ala 195 200 205Thr Glu Gln Gln Arg His Glu Ala Arg Gly Leu Pro Glu Ser Phe Asp 210 215 220Trp Arg Asn Val Asp Gly Ile Asn Tyr Val Ser Pro Val Arg Asn Gln225 230 235 240Gly Asn Cys Gly Ser Cys Tyr Ala Phe Ala Ser Met Ala Met Leu Glu 245 250 255Ala Arg Ile Arg Ile Ala Thr Asn Asn Thr Ala Lys Pro Val Phe Ser 260 265 270Pro Gln Glu Val Val Asp Cys Ser Glu Tyr Ser Gln Gly Cys Asp Gly 275 280 285Gly Phe Gly Tyr Leu Ile Ala Gly Lys Tyr Ala Gln Asp Phe Gly Val 290 295 300Val Glu Glu Ser Cys Tyr Pro Tyr Lys Ala Tyr Thr Gly Lys Cys Lys305 310 315 320Leu Asp Tyr Asn Thr Thr Ala Lys Cys Gln Gln Arg Thr Tyr Thr Ile 325 330 335Lys Tyr Asn Tyr Leu Gly Gly Tyr Phe Gly Ala Cys Asn Glu Glu Ala 340 345 350Met Arg Ile Glu Leu Val Lys Asn Gly Pro Ile Ala Val Gly Phe Glu 355 360 365Val Tyr Lys Asp Phe Met Thr Tyr Arg Arg Gly Ile Tyr Ser His Asp 370 375 380Ser Asp Tyr Glu Thr Glu Gln Lys Val Gly Val Glu Phe Asn Pro Phe385 390 395 400Val Leu Thr Asn His Ala Val Leu Ile Val Gly Tyr Gly Arg Asp Glu 405 410 415Lys Ser Gly Glu Asn Tyr Trp Ile Val Lys Asn Ser Trp Gly Glu Gln 420 425 430Trp Gly Ile Asp Gly Gly Tyr Phe Leu Ile Arg Arg Gly Thr Asn Glu 435 440 445Cys Gly Ile Glu Ser Ile Ala Met Ala Ala Thr Pro Ile Pro Asn 450 455 46037474PRTDermatophagoides pteronyssinus 37Asp Thr Pro Ala Asn Cys Thr Tyr Glu Asp Ile Lys Gly Leu Trp Leu1 5 10 15Phe Glu Glu Thr Glu Pro Ile Lys Asp Arg Trp Glu Lys Cys Pro Glu 20 25 30His Gln Gln Gln Arg Glu Lys Tyr Ser Lys Lys Ile Phe Ile Arg Leu 35 40 45Asp Phe Pro Asn Val Ala Val Asp Lys Phe Gly Asn Ile Gly Glu Trp 50 55 60Thr Met Ile Tyr Asn Gln Gly Phe Glu Val Lys Ile Asn Tyr Arg Lys65 70 75 80Tyr Phe Ala Phe Ser Ala Tyr Glu Arg Lys Ser Glu Asn Asn Val Leu 85 90 95Ser Tyr Cys His Lys Thr Gln Pro Gly Trp Ser His Asp Val Leu Gly 100 105 110Asn Asn Trp Ala Cys Tyr Val Gly His Lys Val Asn Asn Trp Asn Asp 115 120 125Asp Asp Val Ser Lys Thr Thr Thr Val Gly Ala Glu Lys Phe Pro Val 130 135 140Lys Gln His Ser Glu Arg Glu Leu Tyr Leu Gln Asn Ile Asn Val Glu145 150 155 160His Ile Leu Ser Gln Lys His Ile Asp His Leu Asn Ser Gln Gln Lys 165 170 175Ser Trp Lys Ala Ile Val Tyr Pro Asp Leu Gln Ser Lys Ser Ile Glu 180 185 190His Leu Ile Gln Met Ala Gly Gly Arg Lys Ser Arg Ile Ile Asn Arg 195 200 205Pro Lys Pro Leu Arg Ala Thr Glu Gln Gln Lys Gln Leu Ala Arg Ser 210 215 220Leu Pro Glu Ser Phe Asp Trp Arg Asn Leu Asn Gly Ile Asp Tyr Val225 230 235 240Ser Pro Val Arg Asp Gln Gly Lys Cys Gly Ser Cys Tyr Thr Phe Ala 245 250 255Ser Met Ala Met Leu Glu Ser Arg Ile Arg Ile Gln Thr Asn Asn Thr 260 265 270Phe Lys Pro Ile Phe Ser Thr Gln Glu Val Val Asp Cys Ser Glu Tyr 275 280 285Ser Gln Gly Cys Asp Gly Gly Phe Ser Tyr Leu Ile Ala Gly Lys Tyr 290 295 300Ala Gln Asp Phe Gly Val Ile Asp Glu Ser Cys Tyr Pro Tyr Lys Gly305 310 315 320Val Thr Gly Lys Cys Gln Asn Gln Gln Asn Phe Asn Gln Thr Asn Glu 325 330 335Lys Cys Lys Gln Arg Thr Tyr Thr Ile Asp Tyr Lys Tyr Val Gly Gly 340 345 350Tyr Phe Gly Ala Cys Asn Glu Glu Ala Met Gln Ile Glu Leu Val Gln 355 360 365Asn Gly Pro Ile Ala Val Gly Phe Glu Val Tyr Gly Asp Phe Phe Gly 370 375 380Tyr Ser Glu Gly Ile Tyr Ser His Gln Pro Ser Asn Glu Ser Asn Asp385 390 395 400Gln His Gln Gln Ile Lys Ala Glu Phe Asn Pro Phe Glu Met Thr Asn 405 410 415His Ala Val Leu Ile Val Gly Tyr Gly Lys Asp Lys Lys Thr Gly Glu

420 425 430Lys Tyr Trp Ile Val Lys Asn Ser Trp Gly Lys Gln Trp Gly Met Asp 435 440 445Gly Tyr Phe Trp Met Arg Arg Gly Thr Asp Glu Cys Ala Ile Glu Ser 450 455 460Leu Ala Met Ala Ala Thr Pro Ile Pro Asn465 47038509PRTDermatophagoides farinae 38Gln Ser Arg Asp Arg Asn Asp Lys Pro Tyr Arg Ile Val Cys Tyr Trp1 5 10 15Gly Thr Trp Ala Phe Tyr Arg Pro Ala Ser Gly Lys Phe Gln Ala Glu 20 25 30Asn Val Asn Pro Asn Leu Cys Thr His Ile Met Tyr Gly Phe Ala Lys 35 40 45Leu Gln Asn Asn Lys Ile Ala Leu Tyr Asp Pro Asp Leu Asp Asp Gly 50 55 60Asp Glu Asp Trp Asn Ser Gly Leu Gln Trp Gly His Gly Met Ile Arg65 70 75 80Arg Met Val Asn Leu Arg Thr Tyr Asn Pro His Leu Thr Thr Met Ile 85 90 95Ser Leu Gly Gly Trp Asn Glu Gly Ser Asp Lys Tyr Ser Ile Met Val 100 105 110Arg Asp Pro Ala Ser Arg Lys Ile Phe Ile Gln Ser Val Leu His Leu 115 120 125Leu Ala Glu Phe Asp Leu Asp Gly Leu Asp Phe Asp Trp Glu Tyr Pro 130 135 140Ala Met Gln Ala Ser Gly Asp Ser Asp Arg Lys Pro Gly Arg Ala Glu145 150 155 160Asp Lys Glu Asp Phe Val Thr Leu Leu Arg Glu Leu His Glu Ala Phe 165 170 175Gln Pro His Gly Tyr Val Leu Ser Ser Ala Val Ser Ala Gly Lys Pro 180 185 190Thr Ile Asp Arg Ala Tyr Asn Ile Pro Glu Val Ser Lys Tyr Leu Asp 195 200 205Phe Ile Asn Leu Met Ser Tyr Asp Tyr His Gly Gly Trp Glu Ser His 210 215 220Thr Gly His Asn Ala Pro Leu Asn Ser Tyr Lys Asn Ala Asn Glu Leu225 230 235 240Asp Lys Glu Phe Thr Val Thr Tyr Ser Val Glu Tyr Trp Leu Asn His 245 250 255Gly Val Asp Pro Lys Lys Leu Val Leu Gly Ile Pro Leu Tyr Gly Arg 260 265 270Thr Phe Thr Leu Ala Gly Ser Glu His Gly Ile Gly Ala Pro Thr Ile 275 280 285Gly Lys Gly Gly Glu Ser Gly Thr Ile Thr Arg Thr Ile Gly Met Leu 290 295 300Gly Tyr Asn Glu Ile Cys Thr Met Ile Lys Gln Gly Trp Gln Leu Tyr305 310 315 320Arg Asp Glu Ile Glu Arg Ile Pro Tyr Ala Val His Ala Asn Gln Trp 325 330 335Ile Gly Tyr Asp Asp Arg Glu Ser Val Asn Glu Lys Leu Asn Leu Leu 340 345 350Met Ala Lys His Leu Gly Gly Ala Met Val Trp Ser Ile Asp Thr Asp 355 360 365Asp Phe Val Gly Asn Cys Val Gly Val Lys Tyr Pro Leu Leu Arg Ser 370 375 380Ile Ser Lys Lys Leu Asn Asn Val Asp Gly Pro Asp Pro Asp Ile Lys385 390 395 400Arg Tyr His Tyr His Thr Ser Thr Ala Lys Pro His Thr Asp Gly Thr 405 410 415Thr Ser Thr His His Asp His Lys Thr Thr Thr Thr Lys His His Lys 420 425 430Thr Thr Gln Pro His His Lys Thr Thr Gln Pro His His Thr Gln Thr 435 440 445Ile Thr Thr Thr Thr Glu Arg Pro His Gly Lys Phe Gln Cys His Gln 450 455 460Ala Gly Phe Phe Ala Asp Pro Glu Asn Pro Arg Lys Phe His Gln Cys465 470 475 480Val Asp Phe Gly Gly His Leu Lys Asp Tyr Glu Phe Met Cys Gly Glu 485 490 495Gly Thr His Tyr Asp Glu Lys Leu His Ile Cys Val Arg 500 50539520PRTDermatophagoides farinae 39Lys Lys Ala Pro Glu Gly Cys Phe Arg Ala Ala Val Leu Asp His Val1 5 10 15His Gln Thr Asn Val Arg Gln Leu Ser Asp Phe Ala Lys Ile Ile Glu 20 25 30Leu Asn Phe Lys Val Tyr Glu Asp Ala Ala Ala Leu Ala Lys Lys Gln 35 40 45Gly Ala Asp Ile Ile Val Phe Pro Glu Asp Gly Leu Ile Tyr Asn Ile 50 55 60Ala Ser Arg Glu Lys Ala Asp Glu Phe Ala Ser Asp Ile Pro Asp Gly65 70 75 80Glu Thr Asn Ala Cys Thr Leu Glu Thr Lys Ser Val Tyr Asn Arg Leu 85 90 95Ala Cys Leu Ala Gln Lys His Glu Ile Phe Val Val Ala Asp Leu Ile 100 105 110Asp Arg Lys Ser Cys Glu Glu Leu Gly Ile Ser Asn Thr Ser Asp Ser 115 120 125Cys Pro Ala Asp Lys Lys Phe Leu Phe Asn Thr Ala Val Leu Phe Asp 130 135 140Arg Gln Gly Lys Leu Leu Gly Arg Tyr His Lys Met His Leu Phe Gly145 150 155 160Glu Met Thr Met Asn Ile Pro Pro Lys Pro Glu Leu Leu Val Ile Asp 165 170 175Thr Glu Leu Gly Arg Leu Gly Met Gln Ile Cys Phe Asp Met Ile Phe 180 185 190Lys Thr Pro Gly His Phe Leu Ala Glu Gln Asn Lys Phe Asp Thr Met 195 200 205Leu Phe Pro Thr Trp Trp Phe Asp Glu Ala Pro Met Leu Ser Ser Ser 210 215 220Gln Tyr Gln Met Ala Trp Ala Phe Gly Asn Asn Val Thr Leu Leu Ala225 230 235 240Ser Asn Ile His Arg Val Glu Leu Gly Ser Arg Gly Ser Gly Ile Tyr 245 250 255Val Gly Pro His Gln Thr Leu Ala Thr Ala Leu Tyr Asp Asp Ser Val 260 265 270Glu Arg Leu Val Leu Ala Asn Val Pro Ile Lys Pro Arg Glu Thr Asp 275 280 285Lys Ser Val Cys Pro Leu Asp Ser Glu Ile Ile Glu Val Pro Gln Gln 290 295 300Ile Pro Ile Pro Asn Ser Val Lys Tyr His His Leu Asn Met Asn Leu305 310 315 320Leu Asp Val Thr Leu Val Glu Leu Ser Ser Lys Asp Ser Glu Phe His 325 330 335Ile Cys Tyr Lys Gly Val Cys Cys Gln Ile Glu Tyr Arg Leu Ala Val 340 345 350Lys Asp Gln Pro Arg Glu Ser Trp Val Asp Arg Val Pro Leu Leu Ala 355 360 365Asn Met Leu Glu Tyr Phe Thr Pro Glu Glu Arg Tyr Tyr Leu Met Val 370 375 380Ala Asn Arg Thr Arg Pro Gly Thr Tyr Arg Trp Thr Glu Glu Ile Cys385 390 395 400Ala Val Val Val Cys Pro Ser Ser Arg Trp Asn Ile Gly Lys Val Glu 405 410 415Lys Asp Cys Ser Gln Phe Gly Ser Asn Gln Glu Leu Asn Ser Arg Phe 420 425 430Val Tyr Ala Lys Leu Arg Gly Ala Phe Ser Glu Ser Thr Ala Val Tyr 435 440 445Pro Ser Ala Val Gly Pro Lys Asn Gln Leu Ile Asn Pro Glu Asn Lys 450 455 460Trp Lys Tyr Trp Lys Val Asn Val Pro Asp Lys Pro Glu His Phe Val465 470 475 480Glu Leu Gly Ala Lys Asp Asn Pro Glu Ser Lys Ala Ile Glu Leu Ser 485 490 495Thr Leu Ala Leu Tyr Gly Arg Asn Tyr Asp Leu Asp Pro Thr Tyr Lys 500 505 510Gln Lys Pro Val Pro Ile Asn Leu 515 52040519PRTDermatophagoides pteronyssinus 40Lys Ser Ala Pro Glu Gly Cys Phe Arg Ala Ala Val Leu Asp His Val1 5 10 15His Gln Thr Asp Ala Arg His Leu Ser Asn Thr Ala Lys Ile Ile Asp 20 25 30Leu Asn Phe Lys Val Tyr Glu Asp Ala Ala Ala Leu Ala Lys Lys Gln 35 40 45Gly Ala Asp Ile Ile Val Phe Pro Glu Asn Gly Leu Ile Tyr Ser Ile 50 55 60Leu Ser Arg Glu Lys Ala Asp Glu Phe Ala Ser Asp Ile Pro Asp Ala65 70 75 80Glu Val Asn Ala Cys Thr Leu Asp Ser Lys Phe Val Tyr Asn Arg Leu 85 90 95Ala Cys Leu Ala Gln Lys His Gln Met Phe Val Val Ala Asp Leu Ile 100 105 110Asp Arg Lys Ser Cys Glu Glu Leu Gly Ile Asn Asn Val Ser Asp Ser 115 120 125Cys Pro Ala Asp Lys Lys Phe Leu Phe Asn Thr Ala Val Leu Phe Asp 130 135 140Arg Gln Gly Lys Leu Leu Gly Arg Tyr His Lys Met His Leu Phe Gly145 150 155 160Glu Ile Ser Met Asn Pro Pro Pro Lys Pro Glu Leu Leu Val Ile Asp 165 170 175Thr Glu Leu Gly Arg Leu Gly Met Gln Ile Cys Phe Asp Met Ile Phe 180 185 190Lys Thr Pro Gly Tyr Leu Leu Ala Gln Glu Asn Lys Phe Asp Thr Met 195 200 205Leu Phe Pro Thr Trp Trp Phe Asp Glu Ser Pro Met Leu Ser Ser Ser 210 215 220Gln Tyr Gln Met Ala Trp Ala Phe Gly Asn Asn Val Thr Leu Leu Ala225 230 235 240Ser Asn Ile His Arg Ile Glu Val Gly Ser Arg Gly Ser Gly Ile Tyr 245 250 255Val Gly Pro His Arg Thr Leu Ala Ala Ala Leu Tyr Asp Asp Ser Val 260 265 270Glu Arg Leu Val Leu Ala Asn Val Pro Ile Lys Pro Lys Glu Thr Asp 275 280 285Gln Ser Ala Cys Pro Leu Asp Ser Glu Ile Ile Glu Val Pro Gln Gln 290 295 300Ile Pro Ile Pro Lys Ser Val Lys Tyr His His Gln Asn Leu Asn Leu305 310 315 320Lys Asp Val Thr Leu Leu Gln Leu Ser Ser Asn Glu Ser Glu Val His 325 330 335Leu Cys His Lys Gly Val Cys Cys Gln Phe Glu Tyr Arg Leu Ala Met 340 345 350Lys Asp Gln Pro Gln Glu Ser Trp Val Asp Arg Val Pro Leu Leu Ala 355 360 365Asn Met Leu His Tyr Leu Thr Pro Glu Glu Arg Tyr Tyr Leu Leu Ile 370 375 380Ala Asn Arg Thr Arg Pro Gly Ala Tyr Pro Trp Ser Glu Glu Phe Cys385 390 395 400Ala Val Val Val Cys Pro Ser Ser Arg Trp Asn Phe Gly Lys Met Gln 405 410 415Lys Asp Cys Ser Lys Ile Gly Ser Asn Gln Glu Leu Ser Ser Arg Phe 420 425 430Val His Ala Lys Leu Arg Gly Lys Phe Ser Glu Asp Thr Ala Val Tyr 435 440 445Pro Ser Ala Val Gly Ser Lys Asn Gln Leu Ile Tyr Pro Glu Asn Lys 450 455 460Trp Lys Phe Trp Lys Val Asn Val Pro Asn Glu Pro Glu Tyr Phe Ile465 470 475 480Glu Leu Gly Ala Lys Asp Asn Ser Glu Ser Arg Ala Met Glu Leu Gly 485 490 495Ala Leu Val Leu Tyr Gly Arg Asn Tyr Asn Arg Asp Pro Arg Tyr Glu 500 505 510Gln Lys Ala Leu Pro Ile Asn 51541887PRTDermatophagoides pteronyssinus 41Leu Asp Ser Asp Pro Met Lys Cys Asn Ser Ile Arg Asn Glu Asp Arg1 5 10 15Ile Asp Cys Asn Pro Asp Pro Pro Ile Ser Lys Glu Ile Cys Glu Gln 20 25 30Arg Gly Cys Cys Trp Asn Ala Gly Asn Asn Thr Asp Asp Gly Asn Leu 35 40 45Ile Ser Arg Ala Leu Pro His Leu Gly Val Pro Ser Cys Tyr Tyr Gly 50 55 60Glu Asn Tyr Ile Gly Tyr Lys Ile Glu Lys Ile Tyr Ile Lys Asp Glu65 70 75 80Asp Leu Ser Met Thr Lys Leu Lys Arg Val Arg Pro Ser Gly Phe Pro 85 90 95Lys Asp Ile Glu Asn Val Asn Ile Glu Ile His Gln Leu Asn Asp Gln 100 105 110Val Leu Arg Leu Lys Phe Ile Asp Ala Asn Gln Lys Arg Tyr Glu Val 115 120 125Pro Thr Pro Lys Leu Asn Ile Pro Ser Val Ser Lys Ser Ser Asn Ser 130 135 140Arg Leu Tyr Ser Thr Glu Ile Ser Gly Ser His Leu Ile Val Arg Arg145 150 155 160Arg Glu Thr Asn Gln Ser Ile Phe Asp Ile Asn Leu Ala Gln Met Val 165 170 175Tyr Ser Asp Gln Leu Ile His Leu Thr Ser Lys Leu Pro Ser Lys Tyr 180 185 190Ile Tyr Gly Ile Gly Glu His Arg Glu Pro Phe Arg Lys Thr Thr Asp 195 200 205Trp Lys Arg Tyr Thr Gln Trp Thr Arg Asp Gln Val Pro Ile Ser Asp 210 215 220His Ala Leu Tyr Gly Ser His Pro Phe Tyr Met Met Val Glu Asn Lys225 230 235 240Thr Lys Leu Ala Ser Gly Val Phe Leu Phe Asn Ser Asn Ala Met Asp 245 250 255Ile Leu Thr Gln Pro Ser Pro Ala Ile Thr Phe Arg Thr Val Gly Gly 260 265 270Ile Leu Asp Phe Phe Ile Phe Phe Gly Pro Lys Pro Glu Gln Val Val 275 280 285Gln Gln Tyr His Asn Leu Ile Gly Leu Pro Ala Met Pro Pro Phe Trp 290 295 300Ser Leu Gly Tyr Gln Gln Cys Arg Tyr Gly Tyr Asn Asn Phe Thr Asn305 310 315 320Leu Asn Gln Thr Tyr Trp Arg Thr Arg Gln Ala Gly Ile Pro Met Asp 325 330 335Val Gln Trp Thr Asp Ile Asp Met Phe Asp Ser Tyr Asn Asp Phe Thr 340 345 350Tyr Asn His Lys Gln Phe Lys Glu Leu Pro Asp Phe Ile Arg Asn Val 355 360 365Leu His Lys Asn Gly Gln Lys Phe Ile Pro Met Phe Asp Cys Gly Ile 370 375 380Ser Ser Gly Glu Lys Ala His Ser Tyr Arg Pro Tyr Asp Tyr Gly Val385 390 395 400Glu Leu Asp Ile Phe Val Lys Asn Ser Ser Lys Gln Ile Phe Asn Gly 405 410 415Lys Val Trp Asn Gly Lys Ser Thr Val Trp Pro Asp Phe Ser His Pro 420 425 430Asn Ala Thr Lys Tyr Trp Ser Lys Met Phe Glu Glu Tyr His Lys Ile 435 440 445Ile Glu Phe Asp Gly Ala Trp Ile Asp Met Asn Glu Pro Ser Asn Phe 450 455 460Tyr Asp Gly Gln Ile Asp Gly Cys Pro Lys Thr Glu Ile Glu Asn Pro465 470 475 480Gln Tyr Val Pro Gly Met Thr Asp Asp Ser Leu Thr Leu Arg His Lys 485 490 495Thr Leu Cys Met Thr Ala Arg His Tyr Asn Asp Gln Leu His Tyr Asn 500 505 510Leu His Asn Leu Tyr Gly Phe Gln Glu Ala Ile Ala Thr Asn Glu Ala 515 520 525Leu Lys Thr Thr Leu Asn Lys Arg Pro Phe Ile Ile Ser Arg Ser Ser 530 535 540Ala Pro Gly His Gly His Trp Ala Ser His Trp Asp Gly Asp Val Ile545 550 555 560Ser Asp Trp Ser Ser Met Arg Trp Thr Ile Pro Ser Ile Leu Asn Phe 565 570 575Asn Leu Phe Gly Val Pro Met Ile Gly Ala Asp Ile Cys Gly Phe Asn 580 585 590Gly Asp Thr Thr Val Glu Leu Cys Arg Arg Trp Tyr Gln Leu Gly Ala 595 600 605Phe Tyr Ser Phe Val Arg Asn His Asn Thr Asp Asn Ala Ile Asp Gln 610 615 620Asp Pro Val Ala Leu Gly Glu Thr Val Val Arg Thr Ala Arg Ser Ala625 630 635 640Leu Thr Tyr Arg Tyr Ala Phe Leu Pro Tyr Leu Tyr Thr Leu Phe Tyr 645 650 655Asn Val His Gln Asn Gly Gly Thr Val Leu Arg Pro Met Phe Phe Glu 660 665 670Phe Pro Asp Asp Asp His Leu Tyr Asp Ile Glu Thr Gln Phe Met Trp 675 680 685Gly Asp Ser Met Leu Ile Ala Pro Ile Leu Tyr Pro Asn Gln Thr Glu 690 695 700Asn Lys Val Tyr Leu Pro Lys Gly Thr Trp His Asn Met Arg Gln Thr705 710 715 720Phe Glu Ser Gln Gly Gln Tyr Phe Thr Ile Lys Asp Ser Leu Asp Asp 725 730 735Ile Asn Tyr Val Phe Phe Arg Ser Gly Ser Ile Ile Pro Ile Gln Gly 740 745 750Pro Gln Asn Asn Thr Glu Met Met Lys Ser Lys Asp Phe Gly Leu Val 755 760 765Val Ile Leu Asp Ser Lys Asn Pro Glu Pro Tyr Ala Lys Gly Ser Leu 770 775 780Tyr Leu Asp Ser Gly Asp Ser Leu Asp Pro Val Lys Lys Gly Glu Tyr785 790 795 800Asn Phe Tyr Asn Phe Glu Val Lys Asn Asn Thr Leu Thr Ile Glu Ser 805 810 815Gln His Leu Gly Tyr Gln Thr Asn Gln Ser Ile Ile Ile Leu Glu Ile 820 825 830Leu Gly Ile Asp Arg Lys Pro Thr Ser Ile Ile Phe Asp Gly Lys Pro 835 840 845Tyr Tyr Gln Phe Ile Tyr Thr Thr Asn Asn Met Leu Ile Ile Gln Thr 850

855 860Lys Leu Ser Ile Phe Asn Asp Asn Asp Lys Ser Lys Lys Ile His Tyr865 870 875 880Gln Phe Glu Trp Lys Phe Asn 88542885PRTDermatophagoides farinae 42Asp Ser Leu Lys Cys Ser Ser Ile Arg Asn Glu Asp Arg Ile Asp Cys1 5 10 15Asn Pro Asp Pro Pro Ile Ser Lys Asn Val Cys Glu Gln Arg Gly Cys 20 25 30Cys Trp Lys Thr Ala Gly Asn Asp Leu Lys Asn Leu Ser Ser Lys Val 35 40 45Leu Pro Asn Leu Asn Val Pro Tyr Cys Tyr Tyr Gly Glu Asn Tyr Ile 50 55 60Gly Tyr Lys Ile Glu Lys His Ser Lys Asn Leu Ile Gln Leu Lys Arg65 70 75 80Asn Arg Ser Ser Gly Phe Ala Arg Asp Ile Glu Asn Ile Asn Ile Glu 85 90 95Ile His Glu Leu Asn Asp Lys Val Ile Arg Leu Lys Phe Ile Asp Ala 100 105 110Asn Lys Lys Arg Tyr Glu Val Pro Ile Pro Lys Leu Asn Leu Pro Ser 115 120 125Thr Thr Ser Ser Ser Ser Ser Asn Ser Arg Leu Tyr Ser Val Glu Leu 130 135 140Asp Gly Ser His Leu Ile Val Arg Arg Arg Glu Thr Asn Gln Ser Ile145 150 155 160Phe Asp Ile Asn Leu Ala Tyr Met Val Tyr Ser Asp Gln Leu Ile His 165 170 175Val Thr Ser Arg Leu Pro Ser Lys Tyr Ile Tyr Gly Leu Gly Glu His 180 185 190Arg Ala Pro Phe Arg Lys Asn Thr Asn Trp Lys Arg Tyr Thr Gln Trp 195 200 205Thr Arg Asp Gln Tyr Pro Val Thr Asp Lys Ala Leu Tyr Gly Asn His 210 215 220Pro Phe Tyr Leu Thr Val Glu Asp Glu Ser Pro Lys Lys Ser Ala Ser225 230 235 240Gly Val Phe Leu Phe Asn Ser Asn Ala Met Asp Ile Ile Thr Gln Pro 245 250 255Ser Pro Ala Ile Thr Phe Arg Thr Ile Gly Gly Ile Leu Asp Phe Phe 260 265 270Val Phe Phe Gly Pro Lys Pro Glu Asp Val Ile Ser Gln Tyr Gln Asn 275 280 285Leu Ile Gly Leu Pro Ala Met Pro Pro Phe Trp Ser Leu Gly Tyr Gln 290 295 300Gln Cys Arg Tyr Gly Tyr Asn Asn Phe Thr Asn Leu Asn Thr Thr Tyr305 310 315 320Thr Arg Asn Arg Ala Val Gly Ile Pro Met Asp Val Gln Trp Thr Asp 325 330 335Ile Asp Ala Phe Asn Ser Asn Asn Asp Phe Thr Tyr Asp His Lys Arg 340 345 350Phe Lys Glu Leu Pro Asp Phe Ile Asn Asn Val Leu His Pro Asn Gly 355 360 365Gln Lys Phe Ile Pro Met Phe Asp Cys Gly Ile Ser Ser Gly Glu Pro 370 375 380Ala Gly Ser Tyr Lys Pro Phe Asp Ser Gly Val Glu Leu Asp Val Phe385 390 395 400Val Lys Asn Ser Ser Asn Lys Ile Phe Arg Gly Lys Val Trp Asn Gly 405 410 415Lys Ser Thr Val Trp Pro Asp Phe Ser His Pro Asn Ala Thr Glu Tyr 420 425 430Trp Met Asp Met Phe Ala Glu Tyr His Lys Thr Ile Ala Phe Asp Gly 435 440 445Ala Trp Leu Asp Met Asn Glu Pro Ser Asn Phe Tyr Asn Gly Glu Glu 450 455 460His Gly Cys Pro Glu Ser Glu Ile Glu Asn Pro Gln Tyr Val Pro Gly465 470 475 480Met Thr Asp Asp Ser Leu Thr Leu Arg His Lys Thr Leu Cys Met Thr 485 490 495Ala Arg His Tyr Asn Asp Gln Leu His Tyr Asn Leu His Asn Leu Tyr 500 505 510Ser Leu Ser Met Ala Met Ala Thr Asn Ala Ala Leu Thr Lys Leu Asn 515 520 525Lys Arg Pro Phe Ile Ile Ser Arg Ala Thr Ala Pro Gly His Gly His 530 535 540Trp Ala Tyr His Trp Asn Gly Asp Ile Leu Ser Asp Trp Ser Ser Met545 550 555 560Arg Trp Thr Ile Pro Ser Ile Leu Asn Phe Asn Met Phe Gly Ile Pro 565 570 575Met Val Gly Ala Asp Ile Cys Gly Phe Gly Gly Asn Thr Ala Glu Glu 580 585 590Leu Cys Ile Arg Trp Tyr Gln Leu Gly Ala Phe Tyr Ser Phe Ala Arg 595 600 605Asn His Asn Asp Ile His Ser Ile Asp Gln Asp Pro Ala Ala Leu Gly 610 615 620Glu Ser Val Ile Arg Ala Ala Arg Ser Ser Leu Gln Tyr Arg Tyr Arg625 630 635 640Phe Leu Ala His Leu Tyr Thr Leu Phe Tyr His Val His Lys Asn Gly 645 650 655Gly Thr Val Leu Arg Pro Met Phe Phe Glu Phe Pro His Asp Glu His 660 665 670Thr Tyr Glu Ile Glu Thr Gln Phe Met Trp Gly Asp Ser Val Leu Ile 675 680 685Ala Pro Ile Leu Tyr Pro Asn Gln Thr Gln His Lys Ile Tyr Leu Pro 690 695 700Lys Gly Thr Trp Tyr Asn Arg Lys Val Ser Phe Glu Ser Gln Gly Gln705 710 715 720Tyr Ile Thr Met Asn Asp Ser Tyr Asp Asp Ile Asp Tyr Val Phe Val 725 730 735Arg Gly Gly Ser Ile Ile Pro Thr Gln Glu Pro His Asp Asn Thr Glu 740 745 750Leu Met Lys Thr Lys Asp Phe Leu Leu Ile Val Ala Leu Asp Asn Gln 755 760 765Thr Ser Tyr Ala Lys Gly Ser Leu Tyr Trp Asp Ser Gly Asp Ser Leu 770 775 780Asn Pro Asp Lys Thr Gly His Tyr Asn Phe Tyr Asn Phe Asp Ala Val785 790 795 800Asn Asn Thr Leu Thr Ile Gln Ser Gln Trp Leu Gly Tyr Gln Thr Thr 805 810 815Gln Asn Ile Asn Phe Ile Asn Ile Leu Gly Val Pro Lys Leu Pro Thr 820 825 830Ser Phe Lys Leu Asn Gly His Val Ser Asp Pro Arg Ile Ile Arg Phe 835 840 845Asn Tyr Asp Glu Gln Thr Asn Ile Leu Thr Val Glu Thr Lys Leu Pro 850 855 860Ile Tyr Asn Gln Asp Ser Ser Ser His Asp Arg Ile His Tyr Gln Phe865 870 875 880Glu Trp Ile Met Glu 88543975PRTDermatophagoides farinae 43Val Val Ile Lys Val Glu Asn Leu Pro Glu Arg Cys Asp Tyr Ser Gln1 5 10 15Cys Pro Lys Trp Asp Pro Asn Asp Ile Asn Val His Leu Val Ala His 20 25 30Thr His Asp Asp Val Gly Trp Leu Lys Thr Val Glu Gln Tyr Tyr Tyr 35 40 45Gly Leu Lys Asn Asp Ile Gln Arg Ala Gly Val Gln Tyr Ile Leu Asp 50 55 60Thr Val Ile Glu Glu Leu Ile Arg Asn Lys Gln Arg Arg Phe Ile Tyr65 70 75 80Val Glu Ile Ala Phe Phe Trp Lys Trp Trp Gln Glu Gln Asp Glu Asp 85 90 95Gln Arg Met Ile Val Arg Glu Leu Val Arg Thr Gly Gln Leu Glu Phe 100 105 110Ile Asn Gly Gly Trp Ser Met Pro Asp Glu Ala Ala Thr His Tyr Asn 115 120 125Ser Leu Ile Asp Gln Ser Thr Trp Gly Leu Arg Gln Leu Asn Asp Thr 130 135 140Phe Gly Lys Cys Gly His Pro Lys Val Thr Trp Gln Ile Asp Pro Phe145 150 155 160Gly His Ser Arg Glu Met Ala Asn Leu Tyr Ala Gln Met Gly Tyr Asp 165 170 175Ala Leu Phe Phe Ala Arg Gln Asp Tyr Gln Asp Arg Glu Asn Arg Met 180 185 190Thr Asn Arg Lys Leu Glu His Val Trp Gln Gly Ser Asp Asp Leu Gly 195 200 205Thr Ala Gly Asp Ile Phe Thr Gly Met Met Phe Ser Gly Tyr Gly Pro 210 215 220Ile Glu Phe Asn Trp Asp Ile Thr Asn Gly Pro Glu Asp Ala Val Val225 230 235 240Asp Asn Pro Glu Ser Glu Glu Tyr Asn Val Pro Asp Lys Ile Arg Arg 245 250 255Phe Val Glu Lys Ala Lys Tyr Phe Ala Gln Tyr Tyr Ala Thr Asn His 260 265 270Phe Met Phe Pro Met Gly Thr Asp Phe Gln Tyr Gly Asp Ala His Thr 275 280 285Trp Phe Lys Asn Leu Asp Lys Leu Ile Lys Ala Val Asn Asn Ala Gly 290 295 300Lys Gly Val Arg Ala Phe Tyr Ser Thr Pro Ser Cys Tyr Ala Arg Ala305 310 315 320Leu Tyr Glu Thr Asn Arg Thr Trp Thr Thr Lys Thr Asp Asp Phe Phe 325 330 335Pro Tyr Ala Ser Asp Glu His Ala Tyr Trp Thr Gly Tyr Phe Thr Ser 340 345 350Arg Pro Ala Leu Lys Arg Met Glu Arg Met Gly Asn Asn Leu Leu Gln 355 360 365Ala Cys Lys Gln Leu Asp Ile Leu Ala Gly Asn Asp Gly Arg Phe Glu 370 375 380Met Asn Ile Thr Arg Leu Arg Glu Ala Met Gly Val Met Gln His His385 390 395 400Asp Ala Val Thr Gly Thr Glu Lys Gln His Val Ala Phe Asn Tyr Ala 405 410 415Lys Met Leu Asp Ser Ala Met Leu Gln Cys Arg His Val Ile Ser Glu 420 425 430Ser Tyr Arg Lys Leu Phe Pro Thr Gln Thr Lys Glu Gln His Glu Phe 435 440 445Cys Pro Tyr Leu Asn Ile Ser Ser Cys Pro Ser Thr Glu Met Gly Glu 450 455 460Ser Arg Thr Ile His Leu Tyr Asn Pro Leu Gly His Arg Leu Val Asn465 470 475 480Arg Thr Ile Arg Val Pro Val Lys Asp Gly Tyr Tyr Tyr Gln Val Arg 485 490 495Asp Gln Asn Asp His Ser Ile Pro Ala Val Leu Ile Ser Ile Pro Glu 500 505 510Phe Val Arg Lys Ile Pro Gly Arg Lys Ser Val Ala Thr Lys Glu Leu 515 520 525Val Phe Arg Val Pro Ile Ile Glu Ser Leu Gly Ile Arg Arg Phe His 530 535 540Met Ile Ala Thr Lys Glu Lys Gln Gln Asp Ser Ala Val Glu Ile Gln545 550 555 560Gly Glu Lys Phe Val Gly His Lys Gly Gln Arg Phe Gln Leu Lys Asp 565 570 575Gly Leu Ile Ile Glu Phe Asp Ser Asn Gly Lys Ile Ala Thr Met Ile 580 585 590Arg Asn Asn Gln Ser Ile Ser Ile Ser Asn Glu Phe Arg Leu Phe His 595 600 605Gly Ala Asp Ile Gly Arg His Ser Gly Ala Tyr Ile Phe Arg Pro Ser 610 615 620Glu Gln Lys Thr Phe Pro Val Thr Glu Lys Met Glu Ala Thr Leu Tyr625 630 635 640Val Asp Gln Lys Phe Gly Ile Val Gln Glu Val His Gln Gln Phe Asp 645 650 655Ser Phe Val Gly Gln Ile Ile Arg Leu Asp Lys Gln Gly Asp Tyr Val 660 665 670Glu Phe Asp Phe Val Val Gly Pro Ile Pro Val Asp Asp Leu Ile Gly 675 680 685Lys Glu Ile Ile Thr Arg Tyr Asn Thr Asn Leu Ala Asn Asp Glu Thr 690 695 700Phe Phe Thr Asp Ser Asn Gly Arg Gln Met Leu Arg Arg Arg Trp Asn705 710 715 720Tyr Arg Pro Ser Trp Lys Tyr Glu Ile Glu Glu Pro Val Ser Gly Asn 725 730 735Tyr Tyr Pro Val Asn Ser Arg Ile Ala Ile Arg Asp Asp Arg Lys Ser 740 745 750Leu Gln Met Thr Ile Met Thr Asp Arg Ser Gln Gly Gly Ser Leu Ser 755 760 765Pro Glu Gln Ile Asn Gly Ser Val Asp Leu Met Val His Arg Arg Leu 770 775 780Leu His Asp Asp Tyr Phe Gly Val Asp Glu Pro Leu Asn Glu Pro Gly785 790 795 800Val Asp Gly His Gly Ile Val Ile Arg Gly Arg His Leu Leu Leu Leu 805 810 815Asp Thr Leu Glu Lys Ala Ala Glu Lys His Arg Pro Leu Ala Gln Glu 820 825 830Met Phe Met Glu Pro Ile Ile Ser Phe Thr Ser Ser Met Glu Lys Asn 835 840 845Gln Pro Ile Tyr Lys Gly Leu Thr Lys Asp Leu Pro Gly Asn Val His 850 855 860Leu Leu Thr Leu Glu Gln Trp His Ser Lys Arg Tyr Leu Leu Arg Leu865 870 875 880Glu His Phe Tyr Gln Arg Phe Glu Asp Pro Ser Leu Ser Asn Pro Ala 885 890 895Thr Val Ser Leu Arg His Leu Phe Gln Ser Phe Glu Ile Thr Ala Val 900 905 910Glu Glu Leu Thr Leu Gly Ala Asn Gln Pro Ile Ser Ala Leu Lys Asn 915 920 925Arg Leu Gln Tyr Arg Tyr Ile Arg Pro Leu Asn Glu Gln Gln Ser Ser 930 935 940Ile Ile Thr Asp Pro Ile Ile Glu Gly Glu Asn Phe Asp Ile His Leu945 950 955 960Glu Pro Met Gln Ile Arg Thr Phe Leu Ile Asp Ile Lys Arg Asn 965 970 97544990PRTDermatophagoides pteronyssinus 44Val Val Ile Lys Val Glu Asn Leu Pro Glu Gln Cys Asp Tyr Thr Gln1 5 10 15Cys Pro Lys Trp Ser Lys Asp Asp Ile Asn Val His Leu Val Ala His 20 25 30Thr His Asp Asp Val Gly Trp Leu Lys Thr Val Glu Gln Tyr Tyr Tyr 35 40 45Gly Leu Lys Asn Asp Ile Gln Arg Ala Gly Val Gln Tyr Ile Leu Asp 50 55 60Thr Met Ile Glu Glu Leu Ile Arg Asn Lys Asp Arg Arg Phe Ile Tyr65 70 75 80Val Glu Ile Ala Phe Phe Trp Lys Trp Trp Gln Glu Gln Asn Glu Glu 85 90 95Gln Arg Met Ile Val Lys Glu Leu Val Arg Thr Gly Gln Leu Glu Phe 100 105 110Ile Asn Gly Gly Trp Ser Met Pro Asp Glu Ala Ala Thr His Tyr Asn 115 120 125Ser Leu Ile Asp Gln Ser Thr Trp Gly Leu Arg Gln Leu Asn Asp Thr 130 135 140Phe Gly Arg Cys Gly His Pro Lys Val Thr Trp Gln Ile Asp Pro Phe145 150 155 160Gly His Ser Lys Glu Met Ala Asn Leu Tyr Ala Gln Met Gly Tyr Asp 165 170 175Ala Leu Phe Phe Ala Arg Gln Asp Tyr Gln Asp Arg Glu Asn Arg Met 180 185 190Ser Asn Arg Thr Leu Glu His Val Trp Gln Gly Ser Asp Asp Leu Gly 195 200 205Glu Ile Gly Asp Ile Phe Thr Gly Met Met Phe Ser Gly Tyr Gly Pro 210 215 220Ile Glu Phe Asn Trp Asp Ile Thr Asn Gly Pro Glu Asp Ala Val Val225 230 235 240Asp Asn Pro Glu Ser Glu Glu Tyr Asn Val Pro Asp Lys Ile Arg Arg 245 250 255Phe Val Glu Lys Ala Lys Tyr Phe Gly Gln Phe Tyr Ala Thr Asn His 260 265 270Phe Met Phe Pro Met Gly Thr Asp Phe Gln Tyr Thr Asp Ala His Thr 275 280 285Trp Phe Lys Asn Leu Asp Lys Leu Ile Asn Ala Val Asn Lys Ala Gly 290 295 300Lys Gly Val Arg Ala Phe Tyr Ser Thr Pro Ser Cys Tyr Ala His Ala305 310 315 320Leu Tyr Glu Gln Asn Arg Thr Trp Thr Thr Lys Thr Asp Asp Phe Phe 325 330 335Pro Tyr Ala Ser Asp Glu His Ala Tyr Trp Thr Gly Tyr Phe Thr Ser 340 345 350Arg Pro Ala Ile Lys Arg Met Glu Arg Ile Gly Asn Asn Leu Leu Gln 355 360 365Ala Cys Lys Gln Leu Asp Val Leu Ala Asp Asn Asn Gly Arg Phe Glu 370 375 380Met Asn Leu Thr Lys Met Arg Glu Ala Met Gly Val Met Gln His His385 390 395 400Asp Ala Val Thr Gly Thr Glu Lys Gln His Val Ala Phe Asn Tyr Ala 405 410 415Lys Met Leu Asp Ser Ala Met Leu Gln Cys Arg His Ile Ile Asn Glu 420 425 430Ser Tyr Lys Lys Leu Leu Pro Lys Ser Ser Thr Ser Glu His Glu Phe 435 440 445Cys Pro Tyr Leu Asn Ile Ser Ser Cys Pro Thr Thr Glu Met Gly Glu 450 455 460Ser Arg Ile Ile Tyr Leu Tyr Asn Pro Leu Gly His Arg Leu Ile Asn465 470 475 480His Thr Val Arg Leu Pro Ile Lys Asn Gly Tyr Tyr Tyr Arg Ile Gln 485 490 495Asp Gln Asn Asn Gln Ser Val Pro Ser Val Leu Val Pro Ile Pro Glu 500 505 510Phe Val Gln Lys Ile Pro Gly Arg Lys Ser Val Ala Thr Lys Glu Leu 515 520 525Val Phe Arg Val Pro Val Ile Glu Pro Leu Gly Ile Thr Thr Met Tyr 530 535 540Met Tyr Val Asp Lys Asn Glu Gln Pro Asn Ser Ala Ile Glu Ile Lys545 550 555 560Gly Glu Asn Pro Asp Asp Asn Asp Asp Lys Ser Lys

Trp Leu Val Leu 565 570 575Thr Lys Asn Leu Ile Val Glu Phe Tyr Ser Asn Gly Thr Ile Ser Arg 580 585 590Ile Ser Ile Asp Lys Leu His Gln Ser Ile Ser Ile Ser Asn Glu Phe 595 600 605Arg Leu Tyr His Gly Ala Gly Gly Thr Gly Arg His Ser Gly Ala Tyr 610 615 620Ile Phe Arg Pro Asn Glu Gln Lys Thr Phe Pro Val Thr Asn Lys Ile625 630 635 640Lys Ser Thr Phe Phe Ile Asp Arg Lys Tyr His Ile Val Gln Glu Val 645 650 655His Gln Gln Phe Asp Ser Ser Phe Val Gly Gln Ile Ile Arg Met Asp 660 665 670Lys Tyr Asn Asp Asn Val Glu Phe Asp Phe Val Val Gly Pro Ile Pro 675 680 685Val Asn Asp Gln Ile Gly Lys Glu Ile Ile Ala Ser Tyr Lys Thr Asp 690 695 700Leu Glu Asn Asp Glu Thr Phe Tyr Thr Asp Ala Asn Gly Arg Gln Met705 710 715 720Leu Arg Arg Arg Trp Asn Tyr Arg Pro Ser Trp Lys Tyr Asn Val Gln 725 730 735Glu Pro Ile Ser Gly Asn Tyr Tyr Pro Val Asn Ser Arg Ile Ala Ile 740 745 750Arg Asp Glu Lys Gln Ser Leu Gln Met Thr Ile Met Thr Asp Arg Ser 755 760 765Gln Gly Gly Ser Leu Ser Pro Glu Gln Ile Asn Gly Ser Ile Asp Ile 770 775 780Met Ile His Arg Arg Leu Leu His Asp Asp Tyr Phe Gly Val Gly Glu785 790 795 800Ala Leu Asn Glu Pro Gly Val Asp Gly His Gly Leu Val Ile Arg Gly 805 810 815Lys His Leu Leu Leu Leu Asn Ser Ile Lys Gln Ser Ala Ser Glu His 820 825 830Arg Pro Leu Ala Gln Gln Met Phe Met Glu Pro Ile Ile Ser Phe Thr 835 840 845Ser Ile Glu Ser Asn Lys Gln Ala Glu Lys Gln Ser Asn Gln Tyr Ile 850 855 860Gly Leu Asn Asn Asp Leu Pro Ser Asn Val His Leu Leu Thr Leu Glu865 870 875 880Gln Trp His Ser Lys Arg Tyr Leu Leu Arg Leu Glu His Phe Tyr Gln 885 890 895Ser Asn Glu Asp Thr Glu Leu Ser Lys Pro Val Lys Leu Ser Leu Arg 900 905 910His Leu Phe Lys Ser Phe Glu Ile Ile Ala Val Glu Glu Leu Thr Leu 915 920 925Gly Ala Asn Gln Pro Ile Ser Ser Leu Lys Asn Arg Leu His Tyr Arg 930 935 940Tyr Asn Arg Pro Leu Glu Gln Arg Gln Gln Gln Gln Ser Ser Leu Leu945 950 955 960Leu Asp Asp Pro Lys Ile Glu Gly Glu Asn Phe Asp Ile His Leu Ser 965 970 975Pro Met Gln Ile Arg Thr Phe Leu Ile Asp Ile Lys Arg Asn 980 985 9904515PRTArtificial sequenceImmunogenic fragment 45Ile Met Arg Ile Leu Cys Cys Lys Ser Arg Lys Val Ala Pro Cys1 5 10 154615PRTArtificial sequenceImmunogenic fragment 46Phe Asn Tyr Leu Pro Val Asp Val Gln Glu Glu Leu Arg Asn Thr1 5 10 154715PRTArtificial sequenceImmunogenic fragment 47Glu Leu Leu Lys Lys Lys Gly Ile Ile Pro Gly Ile Lys Val Asp1 5 10 154815PRTArtificial sequenceImmunogenic fragment 48Glu Gln Tyr Ile Ser Gly Val Ile Leu Phe Asp Glu Thr Val Tyr1 5 10 154915PRTArtificial sequenceImmunogenic fragment 49Lys Gly Ile Ile Pro Gly Ile Lys Val Asp Thr Gly Val Val Thr1 5 10 155015PRTArtificial sequenceImmunogenic fragment 50Phe Ile Met Leu Lys Pro Asp Ala Val Gln Arg Gly Ile Val Gly1 5 10 155115PRTArtificial sequenceImmunogenic fragment 51Arg Gly Ile Val Gly Glu Ile Ile Arg Arg Phe Glu Ala Lys Gly1 5 10 155215PRTArtificial sequenceImmunogenic fragment 52Glu Ile Ile Arg Arg Phe Glu Ala Lys Gly Phe Lys Leu Val Ala1 5 10 155315PRTArtificial sequenceImmunogenic fragment 53Phe Glu Ala Lys Gly Phe Lys Leu Val Ala Met Lys Phe Met Met1 5 10 155415PRTArtificial sequenceImmunogenic fragment 54Phe Lys Leu Val Ala Met Lys Phe Met Met Ala Ser Glu Asp Leu1 5 10 155515PRTArtificial sequenceImmunogenic fragment 55Lys Phe Met Met Ala Ser Glu Asp Leu Leu Lys Lys His Tyr Ala1 5 10 155615PRTArtificial sequenceImmunogenic fragment 56Leu Lys Lys His Tyr Ala Asp Leu Ala Ala Arg Pro Phe Phe Pro1 5 10 155715PRTArtificial sequenceImmunogenic fragment 57Trp Glu Gly Leu Asn Ala Val Lys Thr Gly Arg Val Met Leu Gly1 5 10 155815PRTArtificial sequenceImmunogenic fragment 58Ile Thr Arg Leu Arg Glu Ala Met Gly Val Met Gln His His Asp1 5 10 155915PRTArtificial sequenceImmunogenic fragment 59Gly Thr Glu Lys Gln His Val Ala Phe Asn Tyr Ala Lys Met Leu1 5 10 156015PRTArtificial sequenceImmunogenic fragment 60His Val Ala Phe Asn Tyr Ala Lys Met Leu Asp Ser Ala Met Leu1 5 10 156115PRTArtificial sequenceImmunogenic fragment 61Ala Met Leu Gln Cys Arg His Val Ile Ser Glu Ser Tyr Arg Lys1 5 10 156215PRTArtificial sequenceImmunogenic fragment 62Arg His Ile Ile Asn Glu Ser Tyr Lys Lys Leu Leu Pro Lys Ser1 5 10 156315PRTArtificial sequenceImmunogenic fragment 63Glu Phe Cys Pro Tyr Leu Asn Ile Ser Ser Cys Pro Ser Thr Glu1 5 10 156415PRTArtificial sequenceImmunogenic fragment 64Leu Tyr Asn Pro Leu Gly His Arg Leu Ile Asn His Thr Val Arg1 5 10 156515PRTArtificial sequenceImmunogenic fragment 65Leu Ile Ser Ile Pro Glu Phe Val Arg Lys Ile Pro Gly Arg Lys1 5 10 156615PRTArtificial sequenceImmunogenic fragment 66Ile Val Gln Glu Val His Gln Gln Phe Asp Ser Phe Val Gly Gln1 5 10 156715PRTArtificial sequenceImmunogenic fragment 67Leu Met Val His Arg Arg Leu Leu His Asp Asp Tyr Phe Gly Val1 5 10 156815PRTArtificial sequenceImmunogenic fragment 68Asp Gly His Gly Ile Val Ile Arg Gly Arg His Leu Leu Leu Leu1 5 10 156915PRTArtificial sequenceImmunogenic fragment 69Glu Pro Ile Ile Ser Phe Thr Ser Ile Glu Ser Asn Lys Gln Ala1 5 10 157015PRTArtificial sequenceImmunogenic fragment 70His Ser Lys Arg Tyr Leu Leu Arg Leu Glu His Phe Tyr Gln Arg1 5 10 157115PRTArtificial sequenceImmunogenic fragment 71Leu Leu Arg Leu Glu His Phe Tyr Gln Arg Phe Glu Asp Pro Ser1 5 10 157215PRTArtificial sequenceImmunogenic fragment 72Lys Arg Tyr Leu Leu Arg Leu Glu His Phe Tyr Gln Ser Asn Glu1 5 10 157315PRTArtificial sequenceImmunogenic fragment 73Thr Leu Glu Gln Trp His Ser Lys Arg Tyr Leu Leu Arg Leu Glu1 5 10 157415PRTArtificial sequenceImmunogenic fragment 74Thr Val Ser Leu Arg His Leu Phe Gln Ser Phe Glu Ile Thr Ala1 5 10 157515PRTArtificial sequenceImmunogenic fragment 75Ser Leu Arg His Leu Phe Lys Ser Phe Glu Ile Ile Ala Val Glu1 5 10 157615PRTArtificial sequenceImmunogenic fragment 76Phe Lys Ser Phe Glu Ile Ile Ala Val Glu Glu Leu Thr Leu Gly1 5 10 157715PRTArtificial sequenceImmunogenic fragment 77Ala Asn Gln Pro Ile Ser Ser Leu Lys Asn Arg Leu His Tyr Arg1 5 10 157815PRTArtificial sequenceImmunogenic fragment 78Glu Leu Thr Leu Gly Ala Asn Gln Pro Ile Ser Ser Leu Lys Asn1 5 10 157915PRTArtificial sequenceImmunogenic fragment 79Gly Asn Asp Leu Lys Asn Leu Ser Ser Lys Val Leu Pro Asn Leu1 5 10 158015PRTArtificial sequenceImmunogenic fragment 80Asn Leu Ser Ser Lys Val Leu Pro Asn Leu Asn Val Pro Tyr Cys1 5 10 158115PRTArtificial sequenceImmunogenic fragment 81Asp Asp Gly Asn Leu Ile Ser Arg Ala Leu Pro His Leu Gly Val1 5 10 158215PRTArtificial sequenceImmunogenic fragment 82Tyr Ile Gly Tyr Lys Ile Glu Lys His Ser Lys Asn Leu Ile Gln1 5 10 158315PRTArtificial sequenceImmunogenic fragment 83Asp Leu Ser Met Thr Lys Leu Lys Arg Val Arg Pro Ser Gly Phe1 5 10 158415PRTArtificial sequenceImmunogenic fragment 84Ile His Gln Leu Asn Asp Gln Val Leu Arg Leu Lys Phe Ile Asp1 5 10 158515PRTArtificial sequenceImmunogenic fragment 85Asp Gln Val Leu Arg Leu Lys Phe Ile Asp Ala Asn Gln Lys Arg1 5 10 158615PRTArtificial sequenceImmunogenic fragment 86Arg Leu Tyr Ser Val Glu Leu Asp Gly Ser His Leu Ile Val Arg1 5 10 158715PRTArtificial sequenceImmunogenic fragment 87Gln Ser Ile Phe Asp Ile Asn Leu Ala Tyr Met Val Tyr Ser Asp1 5 10 158815PRTArtificial sequenceImmunogenic fragment 88Met Val Tyr Ser Asp Gln Leu Ile His Val Thr Ser Arg Leu Pro1 5 10 158915PRTArtificial sequenceImmunogenic fragment 89Arg Ala Pro Phe Arg Lys Asn Thr Asn Trp Lys Arg Tyr Thr Gln1 5 10 159015PRTArtificial sequenceImmunogenic fragment 90Thr Lys Leu Ala Ser Gly Val Phe Leu Phe Asn Ser Asn Ala Met1 5 10 159115PRTArtificial sequenceImmunogenic fragment 91Gly Val Phe Leu Phe Asn Ser Asn Ala Met Asp Ile Leu Thr Gln1 5 10 159215PRTArtificial sequenceImmunogenic fragment 92Gly Pro Lys Pro Glu Gln Val Val Gln Gln Tyr His Asn Leu Ile1 5 10 159315PRTArtificial sequenceImmunogenic fragment 93Gln Val Val Gln Gln Tyr His Asn Leu Ile Gly Leu Pro Ala Met1 5 10 159415PRTArtificial sequenceImmunogenic fragment 94Phe Thr Asn Leu Asn Thr Thr Tyr Thr Arg Asn Arg Ala Val Gly1 5 10 159515PRTArtificial sequenceImmunogenic fragment 95Thr Thr Tyr Thr Arg Asn Arg Ala Val Gly Ile Pro Met Asp Val1 5 10 159615PRTArtificial sequenceImmunogenic fragment 96Leu Pro Asp Phe Ile Arg Asn Val Leu His Lys Asn Gly Gln Lys1 5 10 159715PRTArtificial sequenceImmunogenic fragment 97Asn Ala Thr Glu Tyr Trp Met Asp Met Phe Ala Glu Tyr His Lys1 5 10 159815PRTArtificial sequenceImmunogenic fragment 98Trp Met Asp Met Phe Ala Glu Tyr His Lys Thr Ile Ala Phe Asp1 5 10 159915PRTArtificial sequenceImmunogenic fragment 99Ala Glu Tyr His Lys Thr Ile Ala Phe Asp Gly Ala Trp Leu Asp1 5 10 1510015PRTArtificial sequenceImmunogenic fragment 100Thr Leu Arg His Lys Thr Leu Cys Met Thr Ala Arg His Tyr Asn1 5 10 1510115PRTArtificial sequenceImmunogenic fragment 101Arg His Tyr Asn Asp Gln Leu His Tyr Asn Leu His Asn Leu Tyr1 5 10 1510215PRTArtificial sequenceImmunogenic fragment 102Gln Leu His Tyr Asn Leu His Asn Leu Tyr Gly Phe Gln Glu Ala1 5 10 1510315PRTArtificial sequenceImmunogenic fragment 103Gln Leu His Tyr Asn Leu His Asn Leu Tyr Ser Leu Ser Met Ala1 5 10 1510415PRTArtificial sequenceImmunogenic fragment 104Leu His Asn Leu Tyr Ser Leu Ser Met Ala Met Ala Thr Asn Ala1 5 10 1510515PRTArtificial sequenceImmunogenic fragment 105Ser Leu Ser Met Ala Met Ala Thr Asn Ala Ala Leu Thr Lys Leu1 5 10 1510615PRTArtificial sequenceImmunogenic fragment 106Ala Ala Leu Thr Lys Leu Asn Lys Arg Pro Phe Ile Ile Ser Arg1 5 10 1510715PRTArtificial sequenceImmunogenic fragment 107Asn Glu Ala Leu Lys Thr Thr Leu Asn Lys Arg Pro Phe Ile Ile1 5 10 1510815PRTArtificial sequenceImmunogenic fragment 108Asn Lys Arg Pro Phe Ile Ile Ser Arg Ala Thr Ala Pro Gly His1 5 10 1510915PRTArtificial sequenceImmunogenic fragment 109His Trp Asn Gly Asp Ile Leu Ser Asp Trp Ser Ser Met Arg Trp1 5 10 1511015PRTArtificial sequenceImmunogenic fragment 110Ile Leu Ser Asp Trp Ser Ser Met Arg Trp Thr Ile Pro Ser Ile1 5 10 1511115PRTArtificial sequenceImmunogenic fragment 111Ser Ser Met Arg Trp Thr Ile Pro Ser Ile Leu Asn Phe Asn Met1 5 10 1511215PRTArtificial sequenceImmunogenic fragment 112Pro Ser Ile Leu Asn Phe Asn Leu Phe Gly Val Pro Met Ile Gly1 5 10 1511315PRTArtificial sequenceImmunogenic fragment 113Leu Cys Ile Arg Trp Tyr Gln Leu Gly Ala Phe Tyr Ser Phe Ala1 5 10 1511415PRTArtificial sequenceImmunogenic fragment 114Tyr Gln Leu Gly Ala Phe Tyr Ser Phe Ala Arg Asn His Asn Asp1 5 10 1511515PRTArtificial sequenceImmunogenic fragment 115Ala Phe Tyr Ser Phe Val Arg Asn His Asn Thr Asp Asn Ala Ile1 5 10 1511615PRTArtificial sequenceImmunogenic fragment 116Leu Gly Glu Ser Val Ile Arg Ala Ala Arg Ser Ser Leu Gln Tyr1 5 10 1511715PRTArtificial sequenceImmunogenic fragment 117Ile Arg Ala Ala Arg Ser Ser Leu Gln Tyr Arg Tyr Arg Phe Leu1 5 10 1511815PRTArtificial sequenceImmunogenic fragment 118Ser Ser Leu Gln Tyr Arg Tyr Arg Phe Leu Ala His Leu Tyr Thr1 5 10 1511915PRTArtificial sequenceImmunogenic fragment 119Arg Tyr Arg Phe Leu Ala His Leu Tyr Thr Leu Phe Tyr His Val1 5 10 1512015PRTArtificial sequenceImmunogenic fragment 120Ala His Leu Tyr Thr Leu Phe Tyr His Val His Lys Asn Gly Gly1 5 10 1512115PRTArtificial sequenceImmunogenic fragment 121Asp Ile Glu Thr Gln Phe Met Trp Gly Asp Ser Met Leu Ile Ala1 5 10 1512215PRTArtificial sequenceImmunogenic fragment 122Phe Met Trp Gly Asp Ser Met Leu Ile Ala Pro Ile Leu Tyr Pro1 5 10 1512315PRTArtificial sequenceImmunogenic fragment 123Tyr Asp Asp Ile Asp Tyr Val Phe Val Arg Gly Gly Ser Ile Ile1 5 10 1512415PRTArtificial sequenceImmunogenic fragment 124Asp Ile Asn Tyr Val Phe Phe Arg Ser Gly Ser Ile Ile Pro Ile1 5 10 1512515PRTArtificial sequenceImmunogenic fragment 125Phe Phe Arg Ser Gly Ser Ile Ile Pro Ile Gln Gly Pro Gln Asn1 5 10 1512615PRTArtificial sequenceImmunogenic fragment 126Thr Gln Asn Ile Asn Phe Ile Asn Ile Leu Gly Val Pro Lys Leu1 5 10 1512715PRTArtificial sequenceImmunogenic fragment 127Ser Gln His Leu Gly Tyr Gln Thr Asn Gln Ser Ile Ile Ile Leu1 5 10 1512815PRTArtificial sequenceImmunogenic fragment 128Tyr Gln Thr Asn Gln Ser Ile Ile Ile Leu Glu Ile Leu Gly Ile1 5 10 1512915PRTArtificial sequenceImmunogenic fragment 129Ile Asn Ile Leu Gly Val Pro Lys Leu Pro Thr Ser Phe Lys Leu1 5 10 1513015PRTArtificial sequenceImmunogenic fragment 130Ser Ile Ile Phe Asp Gly Lys Pro Tyr Tyr Gln Phe Ile Tyr Thr1 5 10 1513115PRTArtificial sequenceImmunogenic fragment 131Pro Arg Ile Ile Arg Phe Asn Tyr Asp Glu Gln Thr Asn Ile Leu1 5 10 1513215PRTArtificial sequenceImmunogenic fragment 132Gly Lys Pro Tyr Tyr Gln Phe Ile Tyr Thr Thr Asn Asn Met Leu1 5 10 1513315PRTArtificial sequenceImmunogenic fragment 133Gln Phe Ile Tyr Thr Thr Asn Asn Met Leu Ile Ile Gln Thr Lys1 5 10 1513415PRTArtificial

sequenceImmunogenic fragment 134Thr Asn Asn Met Leu Ile Ile Gln Thr Lys Leu Ser Ile Phe Asn1 5 10 1513515PRTArtificial sequenceImmunogenic fragment 135Ile Ile Gln Thr Lys Leu Ser Ile Phe Asn Asp Asn Asp Lys Ser1 5 10 1513615PRTArtificial sequenceImmunogenic fragment 136Asp Lys Ser Lys Lys Ile His Tyr Gln Phe Glu Trp Lys Phe Asn1 5 10 1513715PRTArtificial sequenceImmunogenic fragment 137His Asp Asn Thr Glu Leu Met Lys Thr Lys Asp Phe Leu Leu Ile1 5 10 1513815PRTArtificial sequenceImmunogenic fragment 138Tyr His Asn Leu Ile Gly Leu Pro Ala Met Pro Pro Phe Trp Ser1 5 10 1513915PRTArtificial sequenceImmunogenic fragment 139Glu Leu Asn Phe Lys Val Tyr Glu Asp Ala Ala Ala Leu Ala Lys1 5 10 1514015PRTArtificial sequenceImmunogenic fragment 140Glu Asp Gly Leu Ile Tyr Asn Ile Ala Ser Arg Glu Lys Ala Asp1 5 10 1514115PRTArtificial sequenceImmunogenic fragment 141Lys His Glu Ile Phe Val Val Ala Asp Leu Ile Asp Arg Lys Ser1 5 10 1514215PRTArtificial sequenceImmunogenic fragment 142Asp Lys Lys Phe Leu Phe Asn Thr Ala Val Leu Phe Asp Arg Gln1 5 10 1514315PRTArtificial sequenceImmunogenic fragment 143Phe Asn Thr Ala Val Leu Phe Asp Arg Gln Gly Lys Leu Leu Gly1 5 10 1514415PRTArtificial sequenceImmunogenic fragment 144Arg Tyr His Lys Met His Leu Phe Gly Glu Met Thr Met Asn Ile1 5 10 1514515PRTArtificial sequenceImmunogenic fragment 145Pro Pro Lys Pro Glu Leu Leu Val Ile Asp Thr Glu Leu Gly Arg1 5 10 1514615PRTArtificial sequenceImmunogenic fragment 146Leu Leu Val Ile Asp Thr Glu Leu Gly Arg Leu Gly Met Gln Ile1 5 10 1514715PRTArtificial sequenceImmunogenic fragment 147Leu Gly Met Gln Ile Cys Phe Asp Met Ile Phe Lys Thr Pro Gly1 5 10 1514815PRTArtificial sequenceImmunogenic fragment 148Thr Trp Trp Phe Asp Glu Ala Pro Met Leu Ser Ser Ser Gln Tyr1 5 10 1514915PRTArtificial sequenceImmunogenic fragment 149Ser Ser Ser Gln Tyr Gln Met Ala Trp Ala Phe Gly Asn Asn Val1 5 10 1515015PRTArtificial sequenceImmunogenic fragment 150Glu Leu Asn Ser Arg Phe Val Tyr Ala Lys Leu Arg Gly Ala Phe1 5 10 1515115PRTArtificial sequenceImmunogenic fragment 151Phe Val Tyr Ala Lys Leu Arg Gly Ala Phe Ser Glu Ser Thr Ala1 5 10 1515215PRTArtificial sequenceImmunogenic fragment 152Leu Arg Gly Ala Phe Ser Glu Ser Thr Ala Val Tyr Pro Ser Ala1 5 10 1515315PRTArtificial sequenceImmunogenic fragment 153Gly Thr Trp Ala Phe Tyr Arg Pro Ala Ser Gly Lys Phe Gln Ala1 5 10 1515415PRTArtificial sequenceImmunogenic fragment 154Asn Leu Cys Thr His Ile Met Tyr Gly Phe Ala Lys Leu Gln Asn1 5 10 1515515PRTArtificial sequenceImmunogenic fragment 155Ile Met Tyr Gly Phe Ala Lys Leu Gln Asn Asn Lys Ile Ala Leu1 5 10 1515615PRTArtificial sequenceImmunogenic fragment 156Leu Gln Trp Gly His Gly Met Ile Arg Arg Met Val Asn Leu Arg1 5 10 1515715PRTArtificial sequenceImmunogenic fragment 157Gly Met Ile Arg Arg Met Val Asn Leu Arg Thr Tyr Asn Pro His1 5 10 1515815PRTArtificial sequenceImmunogenic fragment 158Met Val Asn Leu Arg Thr Tyr Asn Pro His Leu Thr Thr Met Ile1 5 10 1515915PRTArtificial sequenceImmunogenic fragment 159Lys Tyr Ser Ile Met Val Arg Asp Pro Ala Ser Arg Lys Ile Phe1 5 10 1516015PRTArtificial sequenceImmunogenic fragment 160Ser Arg Lys Ile Phe Ile Gln Ser Val Leu His Leu Leu Ala Glu1 5 10 1516115PRTArtificial sequenceImmunogenic fragment 161Ile Gln Ser Val Leu His Leu Leu Ala Glu Phe Asp Leu Asp Gly1 5 10 1516215PRTArtificial sequenceImmunogenic fragment 162Lys Glu Asp Phe Val Thr Leu Leu Arg Glu Leu His Glu Ala Phe1 5 10 1516315PRTArtificial sequenceImmunogenic fragment 163Gln Pro His Gly Tyr Val Leu Ser Ser Ala Val Ser Ala Gly Lys1 5 10 1516415PRTArtificial sequenceImmunogenic fragment 164Glu Val Ser Lys Tyr Leu Asp Phe Ile Asn Leu Met Ser Tyr Asp1 5 10 1516515PRTArtificial sequenceImmunogenic fragment 165Leu Asp Phe Ile Asn Leu Met Ser Tyr Asp Tyr His Gly Gly Trp1 5 10 1516615PRTArtificial sequenceImmunogenic fragment 166Lys Glu Phe Thr Val Thr Tyr Ser Val Glu Tyr Trp Leu Asn His1 5 10 1516715PRTArtificial sequenceImmunogenic fragment 167Gly Val Asp Pro Lys Lys Leu Val Leu Gly Ile Pro Leu Tyr Gly1 5 10 1516815PRTArtificial sequenceImmunogenic fragment 168Leu Tyr Gly Arg Thr Phe Thr Leu Ala Gly Ser Glu His Gly Ile1 5 10 1516915PRTArtificial sequenceImmunogenic fragment 169Glu Lys Leu Asn Leu Leu Met Ala Lys His Leu Gly Gly Ala Met1 5 10 1517015PRTArtificial sequenceImmunogenic fragment 170Gly Asn Cys Val Gly Val Lys Tyr Pro Leu Leu Arg Ser Ile Ser1 5 10 1517115PRTArtificial sequenceImmunogenic fragment 171Val Lys Tyr Pro Leu Leu Arg Ser Ile Ser Lys Lys Leu Asn Asn1 5 10 1517215PRTArtificial sequenceImmunogenic fragment 172His Gly Lys Phe Gln Cys His Gln Ala Gly Phe Phe Ala Asp Pro1 5 10 1517315PRTArtificial sequenceImmunogenic fragment 173Gly Leu Trp Leu Phe Glu Glu Ser Thr Pro Ile Asn Asp Arg Thr1 5 10 1517415PRTArtificial sequenceImmunogenic fragment 174Thr Lys Lys Ile Tyr Val Arg Leu Asp Phe Pro Asn Thr Ala Val1 5 10 1517515PRTArtificial sequenceImmunogenic fragment 175Leu Ile Tyr Asn Gln Gly Phe Glu Val Ile Ile Asn Tyr Arg Lys1 5 10 1517615PRTArtificial sequenceImmunogenic fragment 176Gly Phe Glu Val Ile Ile Asn Tyr Arg Lys Tyr Phe Ala Phe Ser1 5 10 1517715PRTArtificial sequenceImmunogenic fragment 177Ile Asn Tyr Arg Lys Tyr Phe Ala Phe Ser Ala Tyr Glu Arg Lys1 5 10 1517815PRTArtificial sequenceImmunogenic fragment 178Tyr Phe Ala Phe Ser Ala Tyr Glu Arg Lys Ser Asn Ser Lys Val1 5 10 1517915PRTArtificial sequenceImmunogenic fragment 179Ala Met Leu Glu Ala Arg Ile Arg Ile Ala Thr Asn Asn Thr Ala1 5 10 1518015PRTArtificial sequenceImmunogenic fragment 180Asp Gly Gly Phe Gly Tyr Leu Ile Ala Gly Lys Tyr Ala Gln Asp1 5 10 1518115PRTArtificial sequenceImmunogenic fragment 181Thr Tyr Thr Ile Lys Tyr Asn Tyr Leu Gly Gly Tyr Phe Gly Ala1 5 10 1518215PRTArtificial sequenceImmunogenic fragment 182Met Arg Ile Glu Leu Val Lys Asn Gly Pro Ile Ala Val Gly Phe1 5 10 1518315PRTArtificial sequenceImmunogenic fragment 183Ile Ala Val Gly Phe Glu Val Tyr Lys Asp Phe Met Thr Tyr Arg1 5 10 1518415PRTArtificial sequenceImmunogenic fragment 184Glu Val Tyr Lys Asp Phe Met Thr Tyr Arg Arg Gly Ile Tyr Ser1 5 10 1518515PRTArtificial sequenceImmunogenic fragment 185Asp Ala Val Val Tyr Tyr Gly Gln Ala Lys Ser Ser Phe Asp Gln1 5 10 1518615PRTArtificial sequenceImmunogenic fragment 186Gly Asp Leu Gly Tyr Val Asn Glu Gln Ser Leu Pro Tyr Leu Lys1 5 10 1518715PRTArtificial sequenceImmunogenic fragment 187His Phe Met Arg Ser Ile Glu Pro Val Ala Ser Lys Val Ala Tyr1 5 10 1518815PRTArtificial sequenceImmunogenic fragment 188Tyr Asp Ser Arg Phe Ser Met Ile Gly Asp Arg Ser Gln Pro Ile1 5 10 1518915PRTArtificial sequenceImmunogenic fragment 189Asn His Phe His Ser Met Thr Ile Gly Pro Ala Thr Ile Ile Leu1 5 10 1519015PRTArtificial sequenceImmunogenic fragment 190Ala Thr Ile Ile Leu Phe Ser Thr Glu Tyr Tyr Tyr Tyr Thr Lys1 5 10 1519115PRTArtificial sequenceImmunogenic fragment 191Lys His Pro Trp Ile Ile Val Met Gly His Arg Pro Leu Tyr Cys1 5 10 1519215PRTArtificial sequenceImmunogenic fragment 192Gln Tyr Gly Leu Glu Asp Leu Phe Phe Lys Tyr Gly Val Asp Ile1 5 10 1519315PRTArtificial sequenceImmunogenic fragment 193Asp Leu Phe Phe Lys Tyr Gly Val Asp Ile Gln Phe Tyr Gly His1 5 10 1519415PRTArtificial sequenceImmunogenic fragment 194Glu His Phe Tyr Ala Arg Leu Phe Pro Ile Tyr Lys Tyr Lys Met1 5 10 1519515PRTArtificial sequenceImmunogenic fragment 195Arg Leu Phe Pro Ile Tyr Lys Tyr Lys Met Tyr Asn Gly Thr Lys1 5 10 1519615PRTArtificial sequenceImmunogenic fragment 196Tyr Lys Tyr Lys Met Tyr Asn Gly Thr Lys Ser Lys Asn Pro Tyr1 5 10 1519715PRTArtificial sequenceImmunogenic fragment 197Pro Glu Phe Asn His Leu Asn Asp Trp Val Ala Glu His Phe Tyr1 5 10 1519815PRTArtificial sequenceImmunogenic fragment 198Ala Glu His Phe Tyr Asp Tyr Gly Tyr Thr Arg Leu Met Phe Glu1 5 10 1519915PRTArtificial sequenceImmunogenic fragment 199Asp Tyr Gly Tyr Thr Arg Leu Met Phe Glu Asp Lys Tyr Arg Ile1 5 10 1520015PRTArtificial sequenceImmunogenic fragment 200Arg Leu Met Phe Glu Asp Lys Tyr Arg Ile Arg Leu Gln Gln Ile1 5 10 1520115PRTArtificial sequenceImmunogenic fragment 201Lys Ile Gly Ile Asn Gly Phe Gly Arg Ile Gly Arg Leu Val Leu1 5 10 1520215PRTArtificial sequenceImmunogenic fragment 202Tyr Asp Phe Ser Gly Lys Val Ala Leu Val Thr Gly Ser Ser Ser1 5 10 1520315PRTArtificial sequenceImmunogenic fragment 203Ile Ala Val Gln Phe Ala Gln Tyr Gly Ala Lys Leu Thr Ile Thr1 5 10 1520415PRTArtificial sequenceImmunogenic fragment 204Val Gly Asp Leu Leu Asp Gln Ser Leu Pro Ala Lys Leu Ile Asn1 5 10 1520515PRTArtificial sequenceImmunogenic fragment 205Asn Val Arg Ala Val Leu Gln Leu Ser Gln Leu Ala Ala Ile His1 5 10 1520615PRTArtificial sequenceImmunogenic fragment 206Leu Gln Leu Ser Gln Leu Ala Ala Ile His Leu Glu Lys Ser Lys1 5 10 1520715PRTArtificial sequenceImmunogenic fragment 207Glu Leu Gly Leu Lys Gly Val Arg Val Asn Ser Ile Asn Pro Gly1 5 10 1520815PRTArtificial sequenceImmunogenic fragment 208Asn His Thr Leu Leu Lys Phe Leu Ala Gln Pro Asp Glu Ile Ala1 5 10 1520915PRTArtificial sequenceImmunogenic fragment 209Met Thr Gly Ser Ile Val Val Ser Asp Thr Gly Ser Leu Leu Val1 5 10 1521015PRTArtificial sequenceImmunogenic fragment 210Lys Ala Val Val Val Leu Lys Gly Glu Pro Asn Val Thr Gly Thr1 5 10 1521115PRTArtificial sequenceImmunogenic fragment 211Val Ala Asn Val Val Ile Glu Asp Ser Leu Ile Ser Leu Thr Gly1 5 10 1521215PRTArtificial sequenceImmunogenic fragment 212Ile Glu Asp Ser Leu Ile Ser Leu Thr Gly Glu Arg Ser Ile Val1 5 10 1521315PRTArtificial sequenceImmunogenic fragment 213Ile Ser Leu Thr Gly Glu Arg Ser Ile Val Gly Arg Ser Leu Val1 5 10 1521415PRTArtificial sequenceImmunogenic fragment 214Glu Lys Ser Ile Val Gly Arg Ser Leu Val Val His Ala Asp Pro1 5 10 1521515PRTArtificial sequenceImmunogenic fragment 215Tyr Cys Asn Gly Ala Ala Ile Val Ser Ala Ala Arg Ser Gln Ile1 5 10 1521615PRTArtificial sequenceImmunogenic fragment 216Ala Ile Val Ser Ala Ala Arg Ser Gln Ile Gly Val Pro Tyr Ser1 5 10 1521715PRTArtificial sequenceImmunogenic fragment 217Ser Val Tyr Gln Gly Thr His Lys Val Leu Ala Arg Val Ala Ser1 5 10 1521815PRTArtificial sequenceImmunogenic fragment 218Gly Asp Leu Val Phe Phe Gly Asn Pro Ile His His Val Gly Ile1 5 10 1521915PRTArtificial sequenceImmunogenic fragment 219Asn Pro Ile His His Val Gly Ile Val Ser Ala His Gly Arg Met1 5 10 1522015PRTArtificial sequenceImmunogenic fragment 220Val Gly Ile Val Ser Ala His Gly Arg Met Ile Asn Ala Pro His1 5 10 1522115PRTArtificial sequenceImmunogenic fragment 221Leu Lys Pro Glu Phe Leu Lys Val Asn Pro Phe His Lys Ile Pro1 5 10 1522215PRTArtificial sequenceImmunogenic fragment 222Leu Lys Val Asn Pro Phe His Lys Ile Pro Thr Phe Val Asp Thr1 5 10 1522315PRTArtificial sequenceImmunogenic fragment 223Phe His Lys Ile Pro Thr Phe Val Asp Thr Asp Gly Phe Thr Ile1 5 10 1522415PRTArtificial sequenceImmunogenic fragment 224Asp Gly Phe Thr Ile Asp Glu Ser Arg Val Ile Ala Met Tyr Leu1 5 10 1522515PRTArtificial sequenceImmunogenic fragment 225Gln Ile Thr Leu Ala Asp Ile Ala Met Tyr Phe Ser Cys Asn Thr1 5 10 1522615PRTArtificial sequenceImmunogenic fragment 226Asp Ile Ala Met Tyr Phe Ser Cys Asn Thr Met Glu Ile Tyr Ser1 5 10 1522715PRTArtificial sequenceImmunogenic fragment 227Asp Thr Lys Glu Ile Arg Trp Tyr Met Asp Gly Asn Lys Tyr Phe1 5 10 1522815PRTArtificial sequenceImmunogenic fragment 228Gln Lys His Thr Met Glu Ile Asp Tyr Val Arg Val Tyr Gln Trp1 5 10 1522915PRTArtificial sequenceImmunogenic fragment 229Ser Leu Arg Gly Val Thr Ile Arg Asn Ala Pro Phe Leu Glu Glu1 5 10 1523015PRTArtificial sequenceImmunogenic fragment 230Glu Ala Arg Glu Asn Tyr Ile Thr Phe Thr Glu Pro Phe Met Ile1 5 10 1523115PRTArtificial sequenceImmunogenic fragment 231Tyr Ile Thr Phe Thr Glu Pro Phe Met Ile Asn Gln Leu Ala Ala1 5 10 1523215PRTArtificial sequenceImmunogenic fragment 232Glu Pro Phe Met Ile Asn Gln Leu Ala Ala Leu Ile Arg Arg Glu1 5 10 1523315PRTArtificial sequenceImmunogenic fragment 233His Lys Pro Ile Ile Leu Gly Thr Leu Arg Asn Gly Ala Thr Asn1 5 10 1523415PRTArtificial sequenceImmunogenic fragment 234Leu Gly Thr Leu Arg Asn Gly Ala Thr Asn His Phe Leu Ser Lys1 5 10 1523515PRTArtificial sequenceImmunogenic fragment 235Gly Tyr Ala Phe Ile Met Glu Ser Ser Ser Ala Glu His Glu Ile1 5 10 1523615PRTArtificial sequenceImmunogenic fragment 236Leu Thr Met Leu Leu Asp Trp Arg Asn Leu Tyr Pro Arg Lys Tyr1 5 10 1523715PRTArtificial sequenceImmunogenic fragment 237Asp Trp Arg Asn Leu Tyr Pro Arg Lys Tyr Ala Phe Ala Leu Pro1 5 10 1523815PRTArtificial sequenceImmunogenic fragment 238Tyr Pro Arg Lys Tyr Ala Phe Ala Leu Pro Lys Asp Ser Gln Tyr1 5 10 1523915PRTArtificial sequenceImmunogenic fragment 239Lys Asp Ser Gln Tyr Leu Gln His Phe Asn Asn Ala Ile Lys Gln1 5 10 1524015PRTArtificial sequenceImmunogenic fragment 240Leu Gln His Phe Asn Asn Ala Ile Lys Gln Leu Asn Thr Glu Asp1 5 10 1524115PRTArtificial sequenceImmunogenic fragment 241Asn Lys Phe Thr Val Phe Thr Ser Gly Lys Pro Val Ser Gly Leu1

5 10 1524215PRTArtificial sequenceImmunogenic fragment 242Thr Gly Gly Ile Ser Phe Ala Met Glu Gly Pro Ala Lys Val Glu1 5 10 1524315PRTArtificial sequenceImmunogenic fragment 243Ile Thr Val Ile Tyr Lys Pro Pro Thr Pro Gly Asp Tyr Lys Leu1 5 10 1524415PRTArtificial sequenceImmunogenic fragment 244Gly Asp Tyr Lys Leu His Leu Lys Phe Asn Asp Ile His Leu Pro1 5 10 1524515PRTArtificial sequenceImmunogenic fragment 245Ile Arg Glu Tyr Arg Val Glu Ala Ile Lys Val Met Leu Glu Thr1 5 10 1524615PRTArtificial sequenceImmunogenic fragment 246Val Glu Ala Ile Lys Val Met Leu Glu Thr Asp Arg Lys Leu Leu1 5 10 1524715PRTArtificial sequenceImmunogenic fragment 247Asp Arg Lys Leu Leu Thr Leu Asn Asn Ser Gln Ile Ile Leu Asn1 5 10 1524815PRTArtificial sequenceImmunogenic fragment 248Gln Ile Ile Leu Asn Ile Gln Tyr Gln Lys Lys Lys Ile Arg Cys1 5 10 1524915PRTArtificial sequenceImmunogenic fragment 249Leu Ser Glu Leu Leu Thr Met His Leu Leu Ala Tyr Lys Gln Gly1 5 10 1525015PRTArtificial sequenceImmunogenic fragment 250Gly Pro His His Phe Asn Val Asp Phe Ser Lys Asp Phe His Asn1 5 10 1525115PRTArtificial sequenceImmunogenic fragment 251Trp Ser Asn Ser Ser Ala Lys Lys Leu Leu Lys Asn Asp Ile Asp1 5 10 1525215PRTArtificial sequenceImmunogenic fragment 252Arg Ser Thr Leu Lys Leu Phe Gly Thr Ile Lys Met Phe Met Lys1 5 10 1525315PRTArtificial sequenceImmunogenic fragment 253Leu Phe Gly Thr Ile Lys Met Phe Met Lys Glu Leu Leu Asp Asp1 5 10 1525415PRTArtificial sequenceImmunogenic fragment 254Thr His Phe Ile Asn Ala Ile Val Pro Leu Arg Gln Gln Leu Gly1 5 10 1525515PRTArtificial sequenceImmunogenic fragment 255Ala Ile Val Pro Leu Arg Gln Gln Leu Gly Glu Tyr Val Asp Ile1 5 10 1525615PRTArtificial sequenceImmunogenic fragment 256Glu Tyr Val Asp Ile Asp Leu Val Pro Phe Gly Asn Ala His Ile1 5 10 1525715PRTArtificial sequenceImmunogenic fragment 257Thr Gly Gln Lys Gly Phe Glu Leu Ile Lys Val Met Ala Arg Lys1 5 10 1525815PRTArtificial sequenceImmunogenic fragment 258Phe Glu Leu Ile Lys Val Met Ala Arg Lys Thr Pro Arg His Asn1 5 10 1525915PRTArtificial sequenceImmunogenic fragment 259Tyr Val Pro Trp Thr Thr Val Glu Ser Arg Thr Val Asp Val Asn1 5 10 1526015PRTArtificial sequenceImmunogenic fragment 260Val Asp Leu Val Lys Tyr Ile Cys Asp Asn Tyr Leu Asn Asn Val1 5 10 15261130PRTDermatophagoides farinaemisc_feature(42)..(42)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(71)..(71)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(129)..(129)Xaa is serine, alanine, or 2-aminobutyric acid 261Asp Gly Ser His Ile Val Lys Ala Ala Arg Ser Gln Ile Gly Val Pro1 5 10 15Tyr Ser Trp Gly Gly Gly Gly Ile His Gly Lys Ser Lys Gly Ile Gly 20 25 30Glu Gly Ala Asn Ile Val Gly Phe Asp Xaa Ser Gly Leu Ala Gln Tyr 35 40 45Ser Ile Tyr Gln Gly Thr His Lys Thr Ile Ala Arg Thr Ala Ala Ala 50 55 60Gln Tyr Asn Asp Asn His Xaa His His Val Ala Tyr Gly Ser His Gln65 70 75 80Pro Gly Asp Leu Val Phe Phe Gly Asn Pro Ile Tyr His Val Gly Ile 85 90 95Val Ser Ala His Gly Arg Met Val Asn Ala Pro Lys Pro Gly Thr Lys 100 105 110Val Arg Glu Glu Asn Ile Trp Ser Tyr His Ile Ser His Val Ala Arg 115 120 125Xaa Trp 130262132PRTDermatophagoides farinaemisc_feature(42)..(42)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(86)..(86)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(114)..(114)Xaa is serine, alanine, or 2-aminobutyric acid 262Met Ala Ile Asp Gly Lys Tyr Gln Met Glu Ser Ser Glu His Phe Glu1 5 10 15Glu Phe Val Lys Glu Met Gly Leu Asp Val Asp Met Thr Asn Val Asp 20 25 30Leu Ser Lys Thr Ser Thr Met Glu Ile Xaa Lys Asp Gly Asp Val Tyr 35 40 45His Ile Lys Ser Glu Thr Ala Gly Ile Ala His Glu Ile Lys Phe Lys 50 55 60Val Gly Glu Glu Phe Glu Asp Asp Met Asn Gly His Lys Phe Lys Asn65 70 75 80Val Val Thr Met Glu Xaa Asp Asn Lys Met Val Gln Lys Lys Thr Ser 85 90 95Ala Asp Gly Gly Lys Val Val Asn Val Val Arg Glu Phe Thr Asp Ala 100 105 110Gly Xaa Thr Val Lys Ser Thr Tyr Asn Thr Val Thr Trp Thr Arg Val 115 120 125Tyr Lys Arg Met 130263132PRTDermatophagoides pteronyssinusmisc_feature(42)..(42)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(86)..(86)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(114)..(114)Xaa is serine, alanine, or 2-aminobutyric acid 263Met Ala Ile Asp Gly Lys Tyr Gln Met Glu Ser Ser Glu His Phe Glu1 5 10 15Glu Phe Val Lys Glu Met Gly Leu Asp Val Asp Met Thr Asn Val Asp 20 25 30Leu Ser Lys Thr Ser Thr Met Glu Ile Xaa Lys Asp Gly Asp Val Tyr 35 40 45His Ile Lys Ser Glu Thr Ala Gly Ile Ala His Glu Ile Lys Phe Lys 50 55 60Val Gly Glu Glu Phe Glu Asp Asp Met Asn Gly His Lys Phe Lys Asn65 70 75 80Val Val Thr Met Glu Xaa Asp Asn Lys Met Val Gln Lys Lys Thr Ser 85 90 95Ala Asp Gly Gly Lys Val Val Asn Val Val Arg Glu Phe Thr Asp Ala 100 105 110Gly Xaa Thr Val Lys Ser Thr Tyr Asn Thr Val Thr Trp Thr Arg Val 115 120 125Tyr Lys Arg Met 130264134PRTDermatophagoides pteronyssinusmisc_feature(4)..(4)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(46)..(46)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(75)..(75)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(133)..(133)Xaa is serine, alanine, or 2-aminobutyric acid 264Gln Val Tyr Xaa Asn Gly Ala Ala Ile Val Ser Ala Ala Arg Ser Gln1 5 10 15Ile Gly Val Pro Tyr Ser Trp Gly Gly Gly Gly Ile His Gly Lys Ser 20 25 30Arg Gly Ile Gly Glu Gly Ala Asn Thr Val Gly Phe Asp Xaa Ser Gly 35 40 45Leu Ala Gln Tyr Ser Val Tyr Gln Gly Thr His Lys Val Leu Ala Arg 50 55 60Val Ala Ser Gly Gln Tyr Ser Asp Pro Lys Xaa His His Val Ala Tyr65 70 75 80Gly Ser His Gln Pro Gly Asp Leu Val Phe Phe Gly Asn Pro Ile His 85 90 95His Val Gly Ile Val Ser Ala His Gly Arg Met Ile Asn Ala Pro His 100 105 110Thr Gly Thr Asn Val Arg Glu Glu Asn Ile Trp Ser Asp His Ile Ala 115 120 125Asn Val Ala Arg Xaa Trp 130265152PRTDermatophagoides farinaemisc_feature(56)..(56)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(145)..(145)Xaa is serine, alanine, or 2-aminobutyric acid 265Met Val Lys Ala Val Val Val Leu Lys Gly Glu Pro Asn Val Thr Gly1 5 10 15Thr Ile Phe Phe Glu Gln Gln Asp Asn Gly Pro Val Lys Val Ser Gly 20 25 30Thr Val Gln Gly Leu Lys Ser Gly Leu His Gly Phe His Val His Glu 35 40 45Phe Gly Asp Asn Thr Asn Gly Xaa Thr Ser Ala Gly Ala His Tyr Asn 50 55 60Pro Phe Asn Lys Thr His Gly Ala Pro Ala Asp Glu Glu Arg His Val65 70 75 80Gly Asp Leu Gly Asn Val Glu Ala Asn Asp Ala Gly Ile Ala Asn Val 85 90 95Ala Ile Glu Asp Ser Leu Ile Ser Leu Thr Gly Glu Arg Ser Ile Val 100 105 110Gly Arg Ser Leu Val Val His Ala Asp Pro Asp Asp Leu Gly Arg Gly 115 120 125Gly His Glu Leu Ser Lys Thr Thr Gly Asn Ala Gly Gly Arg Leu Ala 130 135 140Xaa Gly Val Ile Gly Val Thr Lys145 150266152PRTDermatophagoides pteronyssinusmisc_feature(56)..(56)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(145)..(145)Xaa is serine, alanine, or 2-aminobutyric acid 266Met Val Lys Ala Val Val Val Leu Lys Gly Asp Pro Asn Val Ser Gly1 5 10 15Thr Ile Phe Phe Glu Gln Gln Asp Asn Gly Pro Val Lys Val Thr Gly 20 25 30Ser Val Gln Gly Leu Lys Pro Gly Leu His Gly Phe His Val His Glu 35 40 45Phe Gly Asp Asn Thr Asn Gly Xaa Thr Ser Ala Gly Ala His Tyr Asn 50 55 60Pro Leu Asn Lys Thr His Gly Ala Pro Asn Asp Glu Glu Arg His Val65 70 75 80Gly Asp Leu Gly Asn Ile Glu Ala Asn Asp Lys Gly Val Ala Asn Val 85 90 95Val Ile Glu Asp Ser Leu Ile Ser Leu Thr Gly Glu Lys Ser Ile Val 100 105 110Gly Arg Ser Leu Val Val His Ala Asp Pro Asp Asp Leu Gly Arg Gly 115 120 125Gly His Glu Leu Ser Lys Thr Thr Gly Asn Ala Gly Gly Arg Leu Val 130 135 140Xaa Gly Val Ile Gly Val Thr Lys145 150267154PRTDermatophagoides farinaemisc_feature(110)..(110)Xaa is serine, alanine, or 2-aminobutyric acid 267Met Ser Ala Asn Thr Glu Arg Thr Phe Ile Met Leu Lys Pro Asp Ala1 5 10 15Val Gln Arg Gly Ile Val Gly Glu Ile Ile Arg Arg Phe Glu Ala Lys 20 25 30Gly Phe Lys Leu Val Ala Met Lys Phe Met Met Ala Ser Glu Asp Leu 35 40 45Leu Lys Lys His Tyr Ala Asp Leu Ala Ala Arg Pro Phe Phe Pro Gly 50 55 60Leu Ile Lys Tyr Met Gln Met Gly Pro Val Val Pro Met Val Trp Glu65 70 75 80Gly Leu Asn Ala Val Lys Thr Gly Arg Val Met Leu Gly Glu Thr Asn 85 90 95Pro Ala Glu Ser Lys Pro Gly Thr Ile Arg Gly Asp Leu Xaa Ile Gln 100 105 110Thr Gly Arg Asn Ile Ile His Gly Ser Asp Ser Val Glu Thr Ala Lys 115 120 125Arg Glu Ile Asp Leu Trp Phe Arg Pro Glu Glu Leu Val Asp Tyr Lys 130 135 140Pro Ser Gln Tyr Glu Trp Val Tyr Glu Asn145 150268154PRTDermatophagoides pteronyssinusmisc_feature(110)..(110)Xaa is serine, alanine, or 2-aminobutyric acid 268Met Ser Ala Asn Thr Glu Arg Thr Phe Ile Met Leu Lys Pro Asp Ala1 5 10 15Val Gln Arg Gly Ile Val Gly Glu Ile Ile Arg Arg Phe Glu Ala Lys 20 25 30Gly Phe Lys Leu Val Ala Met Lys Phe Met Met Ala Ser Glu Asp Leu 35 40 45Leu Lys Lys His Tyr Ala Asp Leu Ala Ala Arg Pro Phe Phe Pro Gly 50 55 60Leu Ile Lys Tyr Met Gln Met Gly Pro Val Val Pro Met Val Trp Glu65 70 75 80Gly Leu Asn Ala Val Lys Thr Gly Arg Val Met Leu Gly Glu Thr Asn 85 90 95Pro Ala Glu Ser Lys Pro Gly Thr Ile Arg Gly Asp Leu Xaa Ile Gln 100 105 110Thr Gly Arg Asn Ile Ile His Gly Ser Asp Ser Val Glu Thr Ala Lys 115 120 125Arg Glu Ile Asp Leu Trp Phe Arg Pro Glu Glu Leu Val Asn Tyr Lys 130 135 140Pro Ser Gln Tyr Glu Trp Val Tyr Glu Asn145 150269171PRTDermatophagoides farinaemisc_feature(13)..(13)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(16)..(16)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(54)..(54)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(61)..(61)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(69)..(69)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(85)..(85)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(102)..(102)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(116)..(116)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(160)..(160)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(170)..(170)Xaa is serine, alanine, or 2-aminobutyric acid 269Asn Arg Val Ser Val Gly Val Tyr Tyr Glu Thr Ile Xaa Ser Gly Xaa1 5 10 15Arg Thr His Phe Ile Asn Ala Ile Val Pro Leu Arg Gln Gln Leu Gly 20 25 30Glu Tyr Val Asp Ile Asp Leu Val Pro Phe Gly Asn Ala His Ile Tyr 35 40 45Ser Asn Gly Pro Gln Xaa Gln His Gly Ala Leu Glu Xaa Tyr Gly Asn 50 55 60Ala Phe Gln Ala Xaa Ser Leu Asp Met Asn Gly Phe Asp Thr Gly Phe65 70 75 80Lys Leu Val Glu Xaa Met Phe Arg Ser Ser Tyr Tyr Ser Asn Pro Gln 85 90 95Tyr Ser Ala Lys Arg Xaa Ala Gln Gln Leu Asn Leu Asn Tyr Asp Gln 100 105 110Leu His Ser Xaa Ala Thr Gly Gln Lys Gly Phe Glu Leu Ile Lys Val 115 120 125Met Ala Arg Lys Thr Pro Arg His Asn Tyr Val Pro Trp Thr Thr Val 130 135 140Glu Ser Arg Thr Val Asp Val Asn Val Asp Leu Val Lys Tyr Ile Xaa145 150 155 160Asp Asn Tyr Leu Asn Asn Val Pro Ala Xaa Asn 165 170270172PRTDermatophagoides pteronyssinusmisc_feature(14)..(14)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(17)..(17)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(55)..(55)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(62)..(62)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(70)..(70)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(86)..(86)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(103)..(103)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(117)..(117)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(161)..(161)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(171)..(171)Xaa is serine, alanine, or 2-aminobutyric acid 270Thr Gln Arg Val Thr Val Gly Val Tyr Tyr Glu Thr Ile Xaa Pro Gly1 5 10 15Xaa Arg Ser His Phe Ile Gln Ala Ile Val Pro Leu Lys Asn Gln Leu 20 25 30Gly Gln Tyr Val Asn Ile Asp Leu Val Pro Phe Gly Asn Ala His Phe 35 40 45Tyr Ser Asn Gly Pro Gln Xaa Gln His Gly Gln Leu Glu Xaa Tyr Gly 50 55 60Asn Ala Phe Gln Ala Xaa Ser Leu Asp Met Asn Gly Phe Glu Thr Ala65 70 75 80Phe Lys Leu Val Glu Xaa Met Phe Arg Ser Asn Tyr Phe Ser Asn Pro 85 90 95Glu Tyr Ser Ser Lys Gln Xaa Ser Gln Gln Leu Asn Leu Asp Tyr Gln 100 105 110Gln Leu Asp Ser Xaa Ala Asn Gly Gln Lys Gly Leu Gln Leu Ile Arg 115 120 125Glu Met Ala Asn Lys Thr Pro Ser His Gln Tyr Val Pro Trp Thr Thr 130 135 140Val Gln Gly Arg Phe Val Asp Gly Asn Val Asp Leu Val Asp Tyr Ile145 150 155 160Xaa Glu Asn Tyr Leu Asn Gly Val Pro Ala Xaa Asn 165 170271188PRTDermatophagoides farinaemisc_feature(85)..(85)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(123)..(123)Xaa is serine, alanine, or 2-aminobutyric acid 271Met Ser Ile Ser Ala His Gly Gly Gly Leu Val Asn Gly Ile Ala Gly1 5 10 15Met Glu Asn Lys Phe Thr Val Phe Thr Ser Gly Lys Pro Val Ser Gly 20 25 30Leu Thr Val Ala Phe Glu Gly Pro Thr Lys Pro Glu Ile Asn Phe Asn 35 40 45Ser Thr Lys Asp Gly Ser Val Asp Val Gly Tyr Thr Pro Lys Ala Gly 50 55 60Gly Gln Tyr Lys Ile His Ile Lys Tyr Glu Gly Lys Glu Ile Val Gly65 70 75 80Ser Pro Phe Lys Xaa Asn Ile Ser Gly Asp Glu Ala Thr His Arg

Lys 85 90 95Leu Thr Glu Lys Val Lys Val Gly Gly Pro Asn Ile Asn Ala Gly Lys 100 105 110Val Asn Gln Asp Asn Gln Leu Thr Ile Asp Xaa Lys Glu Ala Gly Ile 115 120 125Thr Gly Gly Ile Ser Phe Ala Met Glu Gly Pro Ala Lys Val Glu Val 130 135 140Ser Phe Arg Asn Asn Asn Asp Gly Thr Ile Thr Val Ile Tyr Lys Pro145 150 155 160Pro Thr Pro Gly Asp Tyr Lys Leu His Leu Lys Phe Asn Asp Ile His 165 170 175Leu Pro Gly Ser Pro Tyr Pro Ile Val Val Ala Ala 180 185272188PRTDermatophagoides pteronyssinusmisc_feature(85)..(85)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(123)..(123)Xaa is serine, alanine, or 2-aminobutyric acid 272Met Ser Ile Ser Ala His Gly Gly Gly Leu Val Asn Gly Ile Ala Gly1 5 10 15Met Glu Asn Lys Phe Thr Val Phe Thr Ser Gly Lys Pro Val Ser Gly 20 25 30Leu Thr Val Ala Phe Glu Gly Pro Thr Lys Pro Glu Ile Asn Phe Asn 35 40 45Ser Thr Lys Asp Gly Ser Val Asp Val Gly Tyr Ile Pro Lys Ala Gly 50 55 60Gly Gln Tyr Lys Ile His Ile Lys Tyr Glu Gly Lys Glu Ile Val Gly65 70 75 80Ser Pro Phe Lys Xaa Asn Ile Ser Gly Asp Glu Ser Thr His Arg Lys 85 90 95Leu Thr Glu Lys Val Lys Val Gly Gly Pro Asn Ile Ser Thr Gly Lys 100 105 110Val Asn Gln Asp Asn Gln Leu Thr Ile Asp Xaa Lys Glu Ala Gly Ile 115 120 125Thr Gly Gly Ile Ser Phe Ala Met Glu Gly Pro Ala Lys Val Glu Val 130 135 140Ser Phe Arg Asn Asn Asn Asp Gly Thr Ile Thr Val Ile Tyr Lys Pro145 150 155 160Pro Thr Pro Gly Asp Tyr Lys Leu His Leu Lys Phe Asn Asp Ile His 165 170 175Leu Pro Gly Ser Pro Tyr Pro Ile Val Val Ser Ala 180 185273222PRTDermatophagoides farinaemisc_feature(6)..(6)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(15)..(15)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(43)..(43)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(52)..(52)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(60)..(60)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(85)..(85)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(100)..(100)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(111)..(111)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(136)..(137)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(145)..(145)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(158)..(158)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(182)..(182)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(190)..(190)Xaa is serine, alanine, or 2-aminobutyric acid 273Lys Lys Thr Lys Asp Xaa Asp Val Glu Lys Pro Ile Arg Glu Xaa Leu1 5 10 15Lys Asn Gly Leu Leu Arg Tyr Ser Asp Gly Gln Lys Ile Asn Gln Phe 20 25 30Pro Asp Ser Ile Glu Asp Leu Asn Arg Ala Xaa Glu Glu Leu Lys Lys 35 40 45Ser Glu Thr Xaa Ala Arg Asn Phe Ile Asp Thr Xaa Thr Glu Thr Ser 50 55 60Tyr Glu Lys Arg Ser Leu Asp Ser Leu Leu Asp Gly Ile Gln Arg Val65 70 75 80Leu Lys Arg Leu Xaa Arg Ser Gln Ser Lys Lys Glu Gln Leu Leu Gln 85 90 95Asn Val Gly Xaa Ala Asn Ser Val Val Gln Asp Thr Lys Leu Xaa Leu 100 105 110Lys Asn Tyr Arg Met Leu Val Phe Ala Ala Asn Lys Leu Asn Asp Lys 115 120 125Ser Lys Ile Met Arg Ile Leu Xaa Xaa Lys Ser Arg Lys Val Ala Pro 130 135 140Xaa Ile Gly Glu Ala Met Lys Ser Lys Gly Asn Ala Val Xaa Ser Ala145 150 155 160Lys Asn Ile Asp Tyr Phe Arg Glu Met His Gln Asn Ile Lys Ala Glu 165 170 175Met Thr Ala Val Val Xaa Ser Asp Phe Glu Arg Asp Gln Xaa Glu Asn 180 185 190Val Glu Val Pro Ala Ile Thr Glu Ala Glu Tyr Lys Asp Gln Asn Ile 195 200 205Phe Asn Pro Leu Arg Asp Leu Tyr Lys Lys Val Ile Leu Ala 210 215 220274222PRTDermatophagoides pteronyssinusmisc_feature(6)..(6)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(15)..(15)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(43)..(43)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(52)..(52)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(60)..(60)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(85)..(85)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(100)..(100)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(111)..(111)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(136)..(137)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(145)..(145)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(158)..(158)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(182)..(182)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(190)..(190)Xaa is serine, alanine, or 2-aminobutyric acid 274Lys Lys Ser Pro Asp Xaa Asp Ile Glu Arg Pro Ile Arg Glu Xaa Leu1 5 10 15Lys Asp Gly Leu Leu Arg Tyr Ser Ser Gly Gln Lys Ile Asn Gln Phe 20 25 30Pro Asp Thr Ile Gln Asp Leu Asn Arg Ala Xaa Glu Glu Leu Lys Lys 35 40 45Ser Glu Thr Xaa Ala Arg Thr Phe Ile Asp Thr Xaa Thr Glu Ser Ser 50 55 60Tyr Glu Lys Arg Ser Leu Asp Ser Leu Leu Asp Gly Ile Gln Arg Val65 70 75 80Met Lys Arg Leu Xaa Arg Ser Gln Thr Lys Lys Glu Lys Leu Leu Glu 85 90 95Asn Val Gly Xaa Ala Asn Ser Val Val Gln Asp Thr Lys Gln Xaa Leu 100 105 110Lys Asn Tyr Arg Met Leu Val Phe Ala Ala Asn Lys Leu Asp Asn Lys 115 120 125Asn Lys Ile Met Arg Ile Leu Xaa Xaa Lys Ser Arg Lys Val Ala Pro 130 135 140Xaa Ile Gly Glu Ala Met Lys Ala Lys Gly Thr Ala Val Xaa Ser Ala145 150 155 160Lys Asn Ile Asp Tyr Phe Lys Asp Val His Gln Asn Ile Lys Gln Glu 165 170 175Met Thr Ala Val Val Xaa Ser Asp Phe Glu Arg Asp Gln Xaa Glu Asn 180 185 190Val Asp Val Pro Asn Ile Ser Glu Ser Glu Tyr Lys Asp Gln Asn Ile 195 200 205Phe Asn Pro Leu Arg Asp Leu Tyr Lys Lys Val Ile Leu Gly 210 215 220275228PRTDermatophagoides farinaemisc_feature(15)..(15)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(118)..(118)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(169)..(169)Xaa is serine, alanine, or 2-aminobutyric acid 275Met Ser Lys Pro Thr Phe Tyr Phe His Pro Phe Ser Gly Pro Xaa Arg1 5 10 15Thr Val Ser Thr Val Ala Lys Ile Leu Asn Val Glu Met Glu Met Lys 20 25 30Lys Leu Asp Leu Leu Thr Gln Glu His Leu Lys Pro Glu Phe Leu Lys 35 40 45Val Asn Pro Phe His Lys Ile Pro Thr Phe Val Asp Thr Asp Gly Phe 50 55 60Thr Ile Asp Glu Ser Arg Val Ile Ala Met Tyr Leu Leu Gln Ser Arg65 70 75 80Lys Pro Asp Ser Phe Leu Tyr Pro Asn Asn Asp Leu Lys Lys Arg Thr 85 90 95Gln Ile Asp Arg Trp Leu His Tyr Asp Ile Ser Phe Ala Thr Ile Ile 100 105 110Ser Thr Pro Met Tyr Xaa Lys Phe Arg Gly Lys Pro Val Gln Asp His 115 120 125Gln Val Glu Gln Gly Lys Glu Thr Leu Lys Thr Leu Asp Gly Val Met 130 135 140Ala Ser Phe Gly Gly Lys Phe Leu Thr Gly Ser Asp Gln Ile Thr Leu145 150 155 160Ala Asp Ile Ala Met Tyr Phe Ser Xaa Asn Thr Met Glu Ile Tyr Ser 165 170 175Glu Tyr Phe Lys Phe Asp Asp Tyr Pro Asn Leu Lys Ser Trp Tyr Gln 180 185 190Arg Val Ala Glu Ala Leu Lys Gln Tyr Asp Thr Glu Gly Glu Ile Pro 195 200 205Lys Ala Ile Glu Met Ile Lys Gln Phe Ala Gln Gln Arg Met Ala Glu 210 215 220Ser Ala Lys Gln225276228PRTDermatophagoides pteronyssinusmisc_feature(15)..(15)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(118)..(118)Xaa is serine, alanine, or 2-aminobutyric acid 276Met Ser Lys Pro Ile Phe Tyr Tyr His Pro Phe Ser Gly Pro Xaa Arg1 5 10 15Thr Val Ser Thr Val Ala Lys Ile Leu Asn Val Asp Met Glu Met Lys 20 25 30Lys Leu Asp Leu Leu Thr Lys Glu His Leu Asn Pro Glu Phe Leu Lys 35 40 45Val Asn Pro Phe His Lys Val Pro Thr Phe Val Asp Ser Asp Gly Phe 50 55 60Val Val Asp Glu Ser Arg Val Ile Ala Met Tyr Leu Val Glu Ser Arg65 70 75 80Lys Pro Asp Ser Phe Leu Tyr Pro Lys Asn Asp Leu Lys Lys Arg Ile 85 90 95Gln Ile Asp Arg Trp Leu His Tyr Asp Ile Asn Leu Ser Thr Thr Ile 100 105 110Ser Ala Pro Met Phe Xaa Val Phe Arg Gly His Gln Val Gln Asp Tyr 115 120 125Gln Val Glu Gln Gly Lys Glu Thr Leu Lys Thr Leu Asp Gly Val Met 130 135 140Gln Ser Phe Glu Gly Lys Phe Leu Thr Gly Ala Asp Gln Phe Thr Leu145 150 155 160Ala Asp Ile Ala Met Tyr Phe Ser Leu Asn Thr Met Glu Val Tyr Pro 165 170 175Lys Tyr Phe Lys Phe Asp Asp Tyr Pro Asn Leu Lys Ser Trp Tyr His 180 185 190Arg Val Ala Glu Ala Leu Lys Gln Tyr Asp Thr Glu Gly Thr Ile Pro 195 200 205Lys Ala Ile Glu Thr Met Lys Gln Phe Ile Gln Gln Arg Ala Ala Glu 210 215 220Ala Glu Lys His225277233PRTDermatophagoides farinaemisc_feature(11)..(11)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(88)..(88)Xaa is serine, alanine, or 2-aminobutyric acid 277Glu Ser Leu Phe Ile Tyr Asp Asp Tyr Ser Xaa Gly Ser Tyr Gly His1 5 10 15Asp Val Asn Glu Leu Ile Glu Gln Phe Gln Leu Phe Lys Lys Asn Glu 20 25 30His Asn Gln Asn Glu Ser Ile Glu Ile Ile Gly His Phe Leu Lys Lys 35 40 45Ile Arg Glu Tyr Arg Val Glu Ala Ile Lys Val Met Leu Glu Thr Asp 50 55 60Arg Lys Leu Leu Thr Leu Asn Asn Ser Gln Ile Ile Leu Asn Ile Gln65 70 75 80Tyr Gln Lys Lys Lys Ile Arg Xaa Glu Asn Leu Lys His Leu Ser Glu 85 90 95Leu Leu Thr Met His Leu Leu Ala Tyr Lys Gln Gly Met Phe Asp Phe 100 105 110Ala Glu Glu Ile Asp Pro Asp Val Asn Phe Asp Arg Gln Phe Lys Asn 115 120 125Phe Leu Asp Arg Ser Ser Glu Val Met Asn Ile Asn Glu Phe Ser Asp 130 135 140Ile Glu Lys Lys Trp Ser Asn Ser Ser Ala Lys Lys Leu Leu Lys Asn145 150 155 160Asp Ile Asp Gly Leu Ile Thr Ala Leu Asp Asp Leu Arg Glu Asp Phe 165 170 175Leu Lys Asn Ile Ile Leu Pro Glu Phe Asp Ala Gln Ser Arg Tyr Asp 180 185 190Leu Tyr Phe Ser Ile Gln Asp Gln Ile Asn Ile Arg Ser Thr Leu Lys 195 200 205Leu Phe Gly Thr Ile Lys Met Phe Met Lys Glu Leu Leu Asp Asp Leu 210 215 220Asn Gln Pro Asp Phe Glu Ile Leu Tyr225 230278229PRTDermatophagoides pteronyssinusmisc_feature(12)..(12)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(88)..(88)Xaa is serine, alanine, or 2-aminobutyric acid 278Gln Ser Leu Phe Val Asp Tyr Asn Asp Tyr Ser Xaa Gly Ser Ser Gln1 5 10 15Asn Glu Thr Asn Glu Leu Ile Gln Glu Phe Lys Ile Phe Lys Lys Asn 20 25 30Ile Asn Gly Asn Glu Asn Phe Lys Lys Ile Asn Asp Phe Ile Glu Lys 35 40 45Ala Arg Leu Phe Arg Asp Asn Ala Ala Lys Gln Met Leu Glu Ile Asp 50 55 60Gln Gln Leu Leu Thr Leu Asn Val Ile Gln Ile Ser Gln Arg Ile Lys65 70 75 80Leu Glu Asn Asn Lys Ile Gln Xaa Glu Lys Leu Thr Lys Phe Ser Glu 85 90 95Leu Leu Ser Met Gln Leu Leu Ala Tyr Glu Val Gly Met Phe Glu Phe 100 105 110Ala Glu Glu Ile Asp Pro Asn Ile Asp Phe Asp Arg Lys Met Lys Asn 115 120 125Phe Leu Asp Glu Thr Ser Arg Leu Phe Asn Leu Ala Glu Phe Glu Lys 130 135 140Leu Glu Lys Lys Phe Arg Asn Ala Thr Ser Ile Glu Lys Leu Lys Asn145 150 155 160Tyr Ile Asp Gly Glu Leu Val Ala Leu Asn Asp Tyr Ile Asn Glu Phe 165 170 175Leu Lys Asp Ile Ile Met Ser Glu Phe Thr Val Gln Ser Arg Tyr Tyr 180 185 190Leu Asn Phe Ser Ile Glu Asp Gln Val Gln Ile Asp Ser Thr Leu Met 195 200 205Thr Phe Ser Ala Leu Lys Ile Leu Leu Asn Asp Leu Lys Asp Tyr Leu 210 215 220Glu His Leu Asp Asn225279252PRTDermatophagoides farinae 279Glu Trp Arg Leu Val Trp Gln Asp Glu Phe Asn Gly Asn Gln Leu Asp1 5 10 15Leu Asn Gln Trp Ser Tyr Glu Val Gly Gly Asn Gly Trp Gly Asn Asn 20 25 30Glu Leu Glu Phe Tyr Thr Tyr Asn Arg Thr Glu Asn Ala Arg Ile Glu 35 40 45Asn Gly Asn Leu Val Ile Asp Val Arg Val Glu Asn Tyr Arg Glu Arg 50 55 60Gln Phe Thr Ser Ala Arg Leu His Thr Arg Gln Ala Trp Thr Tyr Gly65 70 75 80Arg Phe Glu Ala Arg Ala Arg Met Pro Tyr Gly His Asn Leu Trp Pro 85 90 95Ala Ile Trp Met Met Pro Gln Asp Ser Ile Tyr Gly Ile Trp Ala Ala 100 105 110Ser Gly Glu Ile Asp Ile Val Glu Tyr Arg Gly Asp Asn Pro Asp Arg 115 120 125Ile Glu Gly Thr Ala His Tyr Gly Gly Thr Trp Pro Asn His Ile Tyr 130 135 140Ser Gly Ser Gly Pro Arg Ser Phe Ser Val Asn Phe Ser Gln Asp Phe145 150 155 160His Thr Phe Ala Leu Glu Trp Asp His Lys Gln Leu Arg Trp Tyr Met 165 170 175Asp Asn Gln Gln Tyr Phe Thr Leu Asp Ile Asp Arg Met Leu Trp Ser 180 185 190Gly Lys Gly Val Asn Pro Tyr Thr Lys Asn Gly Gln Pro Phe Asp Gln 195 200 205Pro Phe His Trp Met Leu Asn Val Ala Val Gly Gly Asn Phe Phe Gly 210 215 220Pro Gly Pro Tyr Val Thr Pro Asp Gln Ala Arg Gln Trp Pro Lys His225 230 235 240Thr Leu Glu Ile Asp Tyr Val Arg Val Tyr Gln Gln 245 250280253PRTDermatophagoides pteronyssinus 280Asn Trp Gln Met Val Trp Gln Asp Glu Phe Asn Gly Gly His Leu Asp1 5 10 15Gln Asn His Trp Glu Phe Glu Thr Gly Gly Gly Gly Trp Gly Asn Asn 20 25 30Glu Leu Glu Phe Tyr Thr Ala Asn Arg Ser Gln Asn Val Arg Val Glu 35 40 45Asn Gly His Leu Val Ile Asp Val Arg Val Glu Ser Tyr Gly Gly Arg 50 55 60Asp Phe Thr Ser Gly Arg Ile His Ser Lys Gln Ala Trp Ala Tyr Gly65 70 75 80Lys Phe Glu Ala Arg Ala Arg Leu Pro Ser Gly His His Leu Trp Pro 85 90 95Ala Ile Trp Met Phe Pro Arg Asp Ser Lys Tyr Gly Pro Trp Ala Ala 100 105 110Ser Gly Glu Ile Asp Ile Met Glu Tyr Arg Gly Asp Val His Asp Lys 115 120 125Ile Glu Gly Thr Ile His Tyr Gly Gly Gln Trp Pro Asn Asn Ile Tyr 130 135 140Thr Gly Ser Gly Pro His His Phe Asn Val Asp Phe Ser Lys Asp Phe145 150 155 160His Asn Phe Ala Val Glu Trp Asp Thr Lys Glu Ile Arg Trp Tyr Met

165 170 175Asp Gly Asn Lys Tyr Phe Ser Val Asn Ile Asp Arg Asn Met Trp Ser 180 185 190Gly Lys Gly Asn Asn Pro Tyr Asn Lys Asn Gly Gln Pro Phe Asp Gln 195 200 205Pro Phe Arg Trp Ile Leu Asn Val Ala Val Gly Gly Asn Phe Phe Gly 210 215 220Pro Gly Pro Tyr Val Thr Pro Asp Gln Ala Arg His Trp Gln Lys His225 230 235 240Thr Met Glu Ile Asp Tyr Val Arg Val Tyr Gln Trp Arg 245 250281261PRTDermatophagoides farinae 281Met Ser Ser Ser Ser Gly Lys Lys Tyr Asp Phe Ser Gly Lys Val Ala1 5 10 15Leu Val Thr Gly Ser Ser Ser Gly Ile Gly Ala Ala Ile Ala Val Gln 20 25 30Phe Ala Gln Tyr Gly Ala Lys Leu Thr Ile Thr Gly Arg Asp Gly Ala 35 40 45Ala Leu Glu Ser Val Ala Lys Lys Ile Glu Ile Glu Ser Gly His Gln 50 55 60Pro Leu Gln Ile Val Gly Asp Leu Leu Asp Gln Ser Leu Pro Ala Lys65 70 75 80Leu Ile Asn Glu Thr Val Ser Lys Phe Gly Arg Leu Asp Phe Leu Val 85 90 95Asn Asn Ala Gly Gly Ser Thr Ala His Arg Glu Leu Asn Asp Glu Lys 100 105 110Leu Met Glu Ala Phe Asp Lys Val Phe Ala Leu Asn Val Arg Ala Val 115 120 125Leu Gln Leu Ser Gln Leu Ala Ala Ile His Leu Glu Lys Ser Lys Gly 130 135 140Asn Ile Ile Asn Ile Ser Ser Ile Val Ser Met Lys Pro Tyr Gly His145 150 155 160Val Tyr Ser Ser Ser Lys Ala Ala Leu Asp Met Ile Thr Lys Thr Leu 165 170 175Ala Lys Glu Leu Gly Leu Lys Gly Val Arg Val Asn Ser Ile Asn Pro 180 185 190Gly Pro Val Ala Thr Gly Phe Leu Arg Ser Val Gly Met Ser Ala Thr 195 200 205Ala Tyr Thr Asp Leu Ala Asp Thr Met Ile Asn His Thr Leu Leu Lys 210 215 220Phe Leu Ala Gln Pro Asp Glu Ile Ala Asn Leu Ala Ser Phe Leu Ala225 230 235 240Ser Asp Asp Ala Arg Asn Met Thr Gly Ser Ile Val Val Ser Asp Thr 245 250 255Gly Ser Leu Leu Val 260282262PRTDermatophagoides pteronyssinusmisc_feature(14)..(14)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(39)..(39)Xaa is serine, alanine, or 2-aminobutyric acid 282Gln Ser Arg Asp Arg Asn Asn Lys Pro Tyr Arg Ile Val Xaa Tyr Trp1 5 10 15Gly Thr Trp Ala Phe Tyr Arg Pro Gly Thr Gly Lys Phe Glu Ala Glu 20 25 30Asn Val Asn Pro Asn Leu Xaa Thr His Leu Met Tyr Gly Phe Ala Lys 35 40 45Leu Gln Asn Asn Lys Ile Ala Leu Tyr Asp Pro Asp Leu Asp Asp Gly 50 55 60Asp Glu Asp Trp Asn Ser Gly Leu Asn Trp Gly His Gly Met Ile Arg65 70 75 80Arg Met Val Asn Leu Arg Thr Tyr Asn Pro His Leu Thr Thr Met Ile 85 90 95Ser Ile Gly Gly Trp Asn Glu Gly Ser Asp Lys Tyr Ser Met Met Val 100 105 110Arg Asp Pro Ser Ser Arg Lys Ile Phe Ile Gln Ser Val Leu Asp Leu 115 120 125Leu Ala Glu Phe Asp Leu Asp Gly Leu Asp Phe Asp Trp Glu Tyr Pro 130 135 140Ser Met Lys Ala Thr Gly Asp Asn Asp Arg Lys Pro Gly Arg Asp Glu145 150 155 160Asp Lys Glu Asp Phe Ile Thr Leu Leu Arg Glu Leu His Glu Ala Phe 165 170 175Gln Pro His Gly Tyr Leu Leu Ser Ser Ala Val Ser Ala Gly Lys Pro 180 185 190Thr Ile Asp Arg Ala Tyr Asn Ile Pro Glu Val Ser Lys Tyr Leu Asp 195 200 205Phe Ile Asn Leu Met Ser Tyr Asp Tyr His Gly Gly Trp Glu Ser His 210 215 220Thr Gly His Asn Ala Pro Leu Asn Ser Tyr Asp Asn Ala Asn Glu Leu225 230 235 240Asp Lys Glu Phe Thr Val Thr Tyr Ser Val Asp Tyr Trp Leu Ser His 245 250 255Gly Val Asp Ala Lys Asn 260283270PRTDermatophagoides farinaemisc_feature(205)..(205)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(260)..(260)Xaa is serine, alanine, or 2-aminobutyric acid 283Ser Pro Ala Gln Arg Pro Ser Leu Arg Gly Val Thr Ile Arg Asn Ala1 5 10 15Pro Phe Leu Glu Glu Ile Asp Gly Lys Phe Lys Gly Phe Ile Pro Asp 20 25 30Leu Met Asp Ala Ile Ala Glu Lys Ala Gly Phe Asp Tyr Thr Leu Tyr 35 40 45Leu Ser Pro Asp Gly Arg Tyr Gly Asn Ala Asp Lys Glu Gly Asn Val 50 55 60Thr Gly Met Ile Gly Glu Val Tyr Asn Lys Lys Ala Asp Phe Ala Ala65 70 75 80Ala Asp Leu Thr Met Thr Glu Ala Arg Glu Asn Tyr Ile Thr Phe Thr 85 90 95Glu Pro Phe Met Ile Asn Gln Leu Ala Ala Leu Ile Arg Arg Glu Asp 100 105 110Ala Glu Gly Met Asn Thr Leu Glu Asp Leu Val Asn Ala Gly Lys Thr 115 120 125Gln Pro Asn His Lys Pro Ile Ile Leu Gly Thr Leu Arg Asn Gly Ala 130 135 140Thr Asn His Phe Leu Ser Lys Ser Asp Asp Pro Leu Ala Lys Lys Met145 150 155 160Tyr Glu Gln Ile Lys Ala Asn Asp Gln Ser Ala Thr Thr Ser Ile Ser 165 170 175Lys Gly Ile Glu Arg Val Asp Lys Gln Gly Gly Tyr Ala Phe Ile Met 180 185 190Glu Ser Ser Ser Ala Glu His Glu Ile Ala Asn Asn Xaa Lys Leu Thr 195 200 205Met Leu Leu Asp Trp Arg Asn Leu Tyr Pro Arg Lys Tyr Ala Phe Ala 210 215 220Leu Pro Lys Asp Ser Gln Tyr Leu Gln His Phe Asn Asn Ala Ile Lys225 230 235 240Gln Leu Asn Thr Glu Asp Lys Ile Ala Glu Leu Arg Arg Lys Tyr Trp 245 250 255Ser Asn Asn Xaa Ser Asn Thr Gln Thr Lys Asn Thr Gly Ala 260 265 270284271PRTDermatophagoides pteronyssinusmisc_feature(206)..(206)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(261)..(261)Xaa is serine, alanine, or 2-aminobutyric acid 284Asp Pro Val Gln Gln Arg Pro Thr Leu Arg Gly Val Thr Val Arg Val1 5 10 15Gly Pro Phe Val Lys Glu Asn Asn Gly Lys Phe Glu Gly Phe Ile Pro 20 25 30Asp Leu Val Gln Ala Ile Ser Glu Lys Val Gly Phe Asp Tyr Thr Leu 35 40 45Tyr Leu Ser Pro Asp Gly Arg Tyr Gly Asn Val Ile Ser Asp Gly Asn 50 55 60Val Thr Gly Met Ile Gly Glu Val Tyr Asn Lys Lys Ala Asp Phe Ala65 70 75 80Ala Ala Asp Leu Thr Met Thr Glu Ala Arg Glu Asn Tyr Ile Thr Phe 85 90 95Thr Glu Pro Phe Met Ile Asn Gln Leu Ala Ala Leu Ile Arg Arg Glu 100 105 110Asp Ala Glu Gly Leu Asn Thr Leu Glu Asp Leu Ala Lys Ala Gln Glu 115 120 125Thr Phe Pro Lys Arg Lys Arg Ile Val Leu Gly Thr Leu Arg Asn Gly 130 135 140Ala Thr Asn Tyr Phe Leu Ser Lys Ser Asp Asp Pro Leu Ala Lys Lys145 150 155 160Ile Tyr Glu Gln Ile Lys Ala Asp Asp Gln Ser Val Val Lys Ser Ile 165 170 175Ser Glu Gly Val Glu Arg Val Asp Lys Gln Gly Gly Tyr Ala Phe Ile 180 185 190Met Glu Ser Ala Ser Ala Glu His Glu Ile Ala Asn Asn Xaa Lys Leu 195 200 205Thr Met Leu Leu Asp Trp Arg Asn Leu Phe Pro Arg Lys Tyr Ala Phe 210 215 220Ala Leu Pro Lys Asp Ser Pro Tyr Leu Glu His Phe Asn Asn Ala Ile225 230 235 240Lys Gln Leu Asn Ser Glu Gly Lys Ile Ala Glu Leu Arg Arg Lys Tyr 245 250 255Trp Ala Asn Asn Xaa Ala Glu Asn Lys Thr Lys Asp Asp Lys Asn 260 265 270285275PRTDermatophagoides pteronyssinus 285Met Ser Ser Ser Ser Gly Lys Lys Tyr Asp Phe Ser Gly Lys Val Ala1 5 10 15Leu Val Thr Gly Ser Ser Ser Gly Ile Gly Ala Ala Ile Ala Leu Gln 20 25 30Phe Ala Gln Tyr Gly Ala Gln Val Thr Ile Thr Gly Arg Asp Ala Ala 35 40 45Ala Leu Glu Ser Val Ala Lys Arg Ile Glu Ala Glu Ser Gly His Gln 50 55 60Pro Leu Gln Ile Val Gly Asn Leu Leu Asp Gln Ser Leu Pro Ala Lys65 70 75 80Leu Ile Asp Gly Thr Ile Ser Lys Tyr Gly Arg Leu Asp Phe Leu Val 85 90 95Asn Asn Ala Gly Phe Ser Thr Gln His Arg Asp Ile His Asp Glu Lys 100 105 110Leu Met Glu Ala Phe Asp Gln Val Tyr Gly Leu Asn Val Arg Ala Val 115 120 125Val Gln Leu Ser Gln Leu Ala Ala Thr His Leu Glu Lys Ser Lys Gly 130 135 140Asn Ile Ile Asn Ile Ser Ser Asn Leu Ser Met Met Pro Val His Ile145 150 155 160Ile Tyr Ser Ser Ser Lys Ala Ala Leu Asp Met Ile Thr Lys Thr Met 165 170 175Ala Met Glu Phe Gly Lys Lys Gly Val Arg Val Asn Ser Ile Asn Pro 180 185 190Gly Pro Val Ala Thr Gln Phe Met Arg Ser Leu Gly Met Pro Val Thr 195 200 205Phe Leu Lys Glu Asn Glu Glu Phe Val Lys Glu Leu Thr Leu Leu Lys 210 215 220Phe Val Ala Gln Pro Val Glu Ile Ala Asn Leu Ala Ser Phe Leu Ala225 230 235 240Ser Asp Asp Ala Arg Asn Met Thr Gly Ser Ile Val Val Asn Asp Thr 245 250 255Gly Ser Leu Leu Ala Pro Arg Val Asp Phe Lys Lys Leu Asp Glu Ile 260 265 270Lys Lys Lys 275286310PRTDermatophagoides farinaemisc_feature(89)..(89)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(117)..(117)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(119)..(120)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(128)..(128)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(151)..(151)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(157)..(157)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(180)..(180)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(189)..(189)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(203)..(203)Xaa is serine, alanine, or 2-aminobutyric acid 286Ser Pro Thr Ser Ile Arg Thr Phe Glu Glu Phe Lys Arg Gln Phe Asn1 5 10 15Lys Gln Tyr Gln Ser Ile Glu His Glu Glu Ile Ala Arg Lys Asn Phe 20 25 30Gln Glu Thr Leu Arg Tyr Val Gln Ala Asn Gln Asp Lys Ala Val Ile 35 40 45Asn Glu Tyr Ala Asp Leu Ser Ala Glu Glu Phe Ala Asp Gly Tyr Leu 50 55 60Met Asn Val Gln Asp Val Gln Asp Leu Glu Ala Glu Met Asp Ala His65 70 75 80Lys Glu Tyr Phe Asp Asp Pro Asp Xaa Lys Leu His Gly Asp Phe Asn 85 90 95Pro Pro Lys Glu Phe Asp Leu Arg Pro His Leu Thr Pro Ile Lys Lys 100 105 110Gln Ile Lys Asn Xaa Gly Xaa Xaa Trp Ala Leu Ser Thr Ile Ser Xaa 115 120 125Val Glu Thr Ala Tyr Leu Ala Gln Lys Asn Val Ser Leu Gln Leu Ser 130 135 140Thr Gln Glu Leu Val Asn Xaa Ala Lys Glu His Gly Xaa Lys Lys Gly145 150 155 160Thr Val Leu Asp Gly Ile Glu Tyr Ile Met Ala Asn Gly Thr Thr Thr 165 170 175Glu Glu Ala Xaa Pro Phe Ile Ser Glu Glu Ser Thr Xaa Asp Gln Ser 180 185 190Lys Lys Pro Arg Tyr Glu Ile Ser Asn Trp Xaa Tyr Phe Lys Pro Val 195 200 205Glu Asp Asp Ile Arg Lys Asn Leu Val Leu Arg Arg Thr Ser Val Ser 210 215 220Val Ser Met Asn Ile Glu Asn Leu Lys Ala Phe Val His Tyr Asp Gly225 230 235 240Ser Phe Val Ile Arg Glu Asn Ser Phe Pro Ser Ile Gly Asn Lys Ser 245 250 255Tyr His Ala Val Asn Ile Val Gly Phe Gly Thr Lys Asp Asp Ile Asp 260 265 270His Trp Ile Val Arg Asn Ser Trp Gly Glu Lys Trp Gly Asp Lys Gly 275 280 285Tyr Phe Tyr Val Glu Arg Asp Ile Asn Leu Trp Gly Ile Lys Asp Trp 290 295 300Ala Phe Thr Thr Ile Val305 310287321PRTDermatophagoides pteronyssinusmisc_feature(94)..(94)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(122)..(122)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(124)..(125)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(156)..(156)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(162)..(162)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(194)..(194)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(208)..(208)Xaa is serine, alanine, or 2-aminobutyric acid 287Ser Pro Thr Gly Trp Asn Ile Arg Thr Phe Glu Gln Phe Lys Ile Gln1 5 10 15Phe Asn Lys His Tyr Asp Ser Ile Glu Gln Glu Glu His Ala Arg Glu 20 25 30Asn Phe Leu Glu Thr Leu Lys Tyr Val Asp Ala Asn Pro Asp Lys Ala 35 40 45Val Ile Asn Glu Phe Ala Asp Leu Ser Ala Glu Glu Phe Ala Asp Gly 50 55 60Tyr Leu Met Ser Glu Glu Ser Met Gln Asp Ser Glu Gln Gln Leu Lys65 70 75 80Leu Leu Arg Ala Gly Tyr Asp Tyr His Asp Asp Pro Glu Xaa Leu Phe 85 90 95Asp Glu Asn Leu Glu Ala Pro Lys Gln Val Asp Leu Arg Pro Asp Leu 100 105 110Ser Pro Ile Met Arg Gln Thr Leu His Xaa Gly Xaa Xaa Trp Ala Ile 115 120 125Ser Pro Ile Ser Ser Ala Glu Ser Ala Tyr Lys Ala Arg Tyr Asn Val 130 135 140Ser Ile Gln Leu Ser Val Gln Glu Leu Val Asn Xaa Ala Val Glu His145 150 155 160Gly Xaa Glu Ile Gly Lys Thr Ala Ile Ala Phe Asn Tyr Leu Val Thr 165 170 175Asn Gly Thr Thr Thr Gln Lys Ala Tyr Pro Tyr Thr Ala Lys Glu Gly 180 185 190Ala Xaa Asn Pro Pro Glu Lys Pro Arg Tyr Thr Leu Glu Asn Trp Xaa 195 200 205Ala Tyr Ile Asp Pro Ser Ile Lys Asn Lys Asn Lys Pro Asp Leu Arg 210 215 220Lys Val Leu Ala Gln Lys Arg Thr Ser Ile Thr Val Gln Ile Ser Ile225 230 235 240Lys Asn Val Lys Ala Phe Ala His His Asn Gly Ser Phe Ile Ile Arg 245 250 255Glu Asn Ser Phe Pro Asp Glu Gly Lys Pro Ser Gly His Ala Ile Asn 260 265 270Ile Val Gly Tyr Gly Thr Lys Asp Gly Val Asp Tyr Trp Ile Val Arg 275 280 285Asn Ser Trp Ser Thr Gly Trp Gly Asp Lys Gly Tyr Phe Tyr Val Glu 290 295 300Arg Gly Val Asn Trp Trp Gly Ile Glu Glu Tyr Ala Phe Ile Ala Thr305 310 315 320Phe288332PRTDermatophagoides farinaemisc_feature(149)..(149)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(153)..(153)Xaa is serine, alanine, or 2-aminobutyric acid 288Met Val Lys Ile Gly Ile Asn Gly Phe Gly Arg Ile Gly Arg Leu Val1 5 10 15Leu Arg Ala Ala Val Lys Lys Gly Val Glu Val Val Ala Val Asn Asp 20 25 30Pro Phe Leu Asp Val Lys Tyr Met Val Tyr Met Phe Lys Phe Asp Ser 35 40 45Thr His Gly Arg Tyr Gln Gly Glu Val Lys Glu Glu Gly Gly Leu Leu 50 55 60Val Val Asp Gly Gln Lys Ile Gln Val Phe Gln Glu Arg Asn Pro Ala65 70 75 80Asp Ile Pro Trp Gly Lys Val Gly Ala Asp Tyr Val Val Glu Ser Thr 85 90 95Gly Val Phe Thr Thr Ile Glu Lys Ala Lys Ala His Leu Ala Gly Gly 100 105 110Ala Lys Lys Val Val Ile Ser Ala Pro Ser Ala Asp Ala Pro Met Tyr 115

120 125Val Met Gly Val Asn His Asp Lys Tyr Asp Pro Ser Gln Gln Ile Ile 130 135 140Ser Asn Ala Ser Xaa Thr Thr Asn Xaa Leu Ala Pro Leu Ala Lys Val145 150 155 160Ile Asn Asp Lys Phe Gly Ile Glu Asn Gly Leu Met Thr Thr Val His 165 170 175Ala Val Thr Ala Thr Gln Lys Thr Val Asp Gly Pro Ser Gly Lys Met 180 185 190Trp Arg Asp Gly Arg Gly Ala Gly Gln Asn Ile Ile Pro Ala Ser Thr 195 200 205Gly Ala Ala Lys Ala Val Gly Lys Val Ile Pro Glu Leu Asn Gly Lys 210 215 220Leu Thr Gly Met Ala Leu Arg Val Pro Val Pro Asp Val Ser Val Val225 230 235 240Asp Leu Thr Val Thr Leu Lys Asn Pro Ala Ser Tyr Asp Glu Ile Lys 245 250 255Ala Ala Ile Lys Ala Ala Ala Glu Ser Asp His Trp Lys Gly Ile Leu 260 265 270Glu Tyr Thr Asp Glu Glu Val Val Ser Ser Asp Phe Ile Ser Asp Thr 275 280 285His Ser Ser Ile Phe Asp Ala Lys Ala Gly Ile Ala Leu Thr Pro Thr 290 295 300Phe Val Lys Leu Ile Ala Trp Tyr Asp Asn Glu Phe Gly Tyr Ser Asn305 310 315 320Arg Val Ile Asp Leu Ile Lys Tyr Val Ala Ser Lys 325 330289332PRTDermatophagoides pteronyssinusmisc_feature(149)..(149)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(153)..(153)Xaa is serine, alanine, or 2-aminobutyric acid 289Met Val Lys Ile Gly Ile Asn Gly Phe Gly Arg Ile Gly Arg Leu Val1 5 10 15Leu Arg Ala Ala Ile Lys Lys Gly Val Glu Val Ala Ala Ile Asn Asp 20 25 30Pro Phe Leu Asp Val Lys Tyr Met Val Tyr Met Phe Lys Phe Asp Ser 35 40 45Thr His Gly Arg Tyr Gln Gly Glu Val Lys Glu Glu Gly Gly Leu Leu 50 55 60Val Val Asp Gly Gln Lys Ile Gln Val Phe Gln Glu Arg Asn Pro Ala65 70 75 80Glu Ile Pro Trp Gly Lys Val Gly Ala Asp Tyr Val Val Glu Ser Thr 85 90 95Gly Val Phe Thr Thr Ile Glu Lys Ala Lys Ala His Leu Ala Gly Gly 100 105 110Ala Lys Lys Val Ile Ile Ser Ala Pro Ser Ala Asp Ala Pro Met Tyr 115 120 125Val Met Gly Val Asn His Asp Lys Tyr Asp Pro Lys Gln Gln Ile Ile 130 135 140Ser Asn Ala Ser Xaa Thr Thr Asn Xaa Leu Ala Pro Leu Ala Lys Val145 150 155 160Ile Asn Asp Lys Phe Gly Ile Glu Asn Gly Leu Met Thr Thr Val His 165 170 175Ala Ile Thr Ala Thr Gln Lys Thr Val Asp Gly Pro Ser Gly Lys Leu 180 185 190Trp Arg Asp Gly Arg Gly Ala Gly Gln Asn Ile Ile Pro Ala Ser Thr 195 200 205Gly Ala Ala Lys Ala Val Gly Lys Val Ile Pro Glu Leu Asn Gly Lys 210 215 220Leu Thr Gly Met Ala Leu Arg Val Pro Val Pro Asp Val Ser Val Val225 230 235 240Asp Leu Thr Val Thr Leu Lys Asn Pro Ala Ser Tyr Asp Glu Ile Lys 245 250 255Ala Ala Val Lys Ala Ala Ala Glu Ser Asp His Trp Lys Gly Ile Leu 260 265 270Glu Tyr Thr Asp Glu Glu Val Val Ser Ser Asp Phe Ile Ser Asp Thr 275 280 285His Ser Ser Ile Phe Asp Ala Lys Ala Gly Ile Ala Leu Thr Pro Thr 290 295 300Phe Val Lys Leu Ile Ala Trp Tyr Asp Asn Glu Phe Gly Tyr Ser Asn305 310 315 320Arg Val Val Asp Leu Ile Lys Tyr Val Ala Ser Lys 325 330290361PRTDermatophagoides farinaemisc_feature(133)..(133)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(141)..(141)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(148)..(148)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(175)..(176)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(200)..(200)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(238)..(238)Xaa is serine, alanine, or 2-aminobutyric acid 290Met Ala Lys Phe Asn Tyr Leu Pro Val Asp Val Gln Glu Glu Leu Arg1 5 10 15Asn Thr Ala Asn Ala Ile Val Ser Val Gly Lys Gly Ile Leu Ala Ala 20 25 30Asp Glu Ser Thr Gly Thr Ile Gly Lys Arg Phe Ala Asp Ile Asn Val 35 40 45Glu Asn Val Glu Pro Asn Arg Arg Ala Tyr Arg Gln Leu Leu Phe Tyr 50 55 60Ser Glu Asn Ile Glu Gln Tyr Ile Ser Gly Val Ile Leu Phe Asp Glu65 70 75 80Thr Val Tyr Gln Lys Asp Asp Asn Asn Thr Pro Phe Pro Glu Leu Leu 85 90 95Lys Lys Lys Gly Ile Ile Pro Gly Ile Lys Val Asp Thr Gly Val Val 100 105 110Thr Leu Gln Gly Thr Asn Gly Glu Ser Thr Thr Gln Gly Leu Asp Asn 115 120 125Leu Thr Lys Arg Xaa Gln Glu Tyr Tyr Asn His Gly Xaa Arg Phe Ala 130 135 140Lys Trp Arg Xaa Val Leu Lys Ile Gly Lys Asp Glu Pro Ser Ala Leu145 150 155 160Ala Ile Leu Glu Asn Ala Asn Val Leu Ala Arg Tyr Ala Ser Xaa Xaa 165 170 175Gln Gln Ala Arg Ile Val Pro Ile Val Glu Pro Glu Ile Leu Pro Asp 180 185 190Gly Asp His Asp Leu Glu Arg Xaa Gln Lys Val Thr Glu Thr Val Leu 195 200 205Ala Ala Val Tyr Lys Ala Leu Asn Asp His His Val Tyr Leu Glu Gly 210 215 220Ser Leu Leu Lys Pro Asn Met Val Thr Pro Gly Gln Ser Xaa Pro Gln225 230 235 240Lys Ala Ser Pro Gln Asp Ile Ala Arg Ala Thr Val Thr Ala Leu Gln 245 250 255Arg Thr Val Pro Ala Ala Val Pro Gly Val Val Phe Leu Ser Gly Gly 260 265 270Gln Ser Glu Glu Glu Ala Ser Val Asn Leu Asn Ala Ile Asn Gln Tyr 275 280 285Gln Gly Lys Lys Pro Trp Ala Leu Ser Phe Ser Tyr Gly Arg Ala Leu 290 295 300Gln Ala Ser Ala Leu Arg Ala Trp Gln Gly Lys Pro Glu Asn Ile Ser305 310 315 320Ala Gly Gln Lys Glu Phe Leu Gln Arg Ala Lys Ala Asn Ser Leu Ser 325 330 335Ala Gln Gly Gln Tyr Thr Gly Gly Val Val Gly Ala Ala Ala Asp Gln 340 345 350Asp Leu Phe Ile Lys Asp His Gln Tyr 355 360291362PRTDermatophagoides pteronyssinusmisc_feature(133)..(133)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(141)..(141)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(148)..(148)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(175)..(176)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(200)..(200)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(238)..(238)Xaa is serine, alanine, or 2-aminobutyric acid 291Met Ala Lys Phe Asn Tyr Leu Pro Val Asp Val Gln Glu Glu Leu Arg1 5 10 15Asn Thr Ala Asn Ala Ile Val Ser Val Gly Lys Gly Ile Leu Ala Ala 20 25 30Asp Glu Ser Thr Gly Thr Ile Gly Lys Arg Phe Ala Asp Ile Asn Val 35 40 45Glu Asn Val Glu Gln Asn Arg Gln Ala Tyr Arg Gln Leu Leu Phe Tyr 50 55 60Ser Glu Gly Ile Glu Gln Tyr Ile Ser Gly Val Ile Leu Phe Asp Glu65 70 75 80Thr Val Tyr Gln Lys Asp Asp Lys Gly Val Pro Phe Pro Glu Leu Leu 85 90 95Lys Lys Lys Gly Ile Ile Pro Gly Ile Lys Val Asp Thr Gly Val Val 100 105 110Thr Leu Gln Gly Thr Asn Gly Glu Ser Thr Thr Gln Gly Leu Asp Asn 115 120 125Leu Thr Lys Arg Xaa Gln Glu Tyr Tyr Asn Gln Gly Xaa Arg Phe Ala 130 135 140Lys Trp Arg Xaa Val Leu Lys Ile Gly Gln Asp Glu Pro Ser Ser Leu145 150 155 160Ala Ile Val Glu Asn Ala Asn Val Leu Ala Arg Tyr Ala Ser Xaa Xaa 165 170 175Gln Gln Ala Arg Ile Val Pro Ile Val Glu Pro Glu Ile Leu Pro Asp 180 185 190Gly Asp His Asn Leu Glu Arg Xaa Gln Lys Val Thr Glu Thr Val Leu 195 200 205Ala Ala Val Tyr Lys Ala Leu Asn Asp His His Val Tyr Leu Glu Gly 210 215 220Thr Leu Leu Lys Pro Asn Met Val Thr Pro Gly Gln Ser Xaa Pro Gln225 230 235 240Lys Ala Ser Pro Gln Glu Val Ala Gln Ala Thr Val Thr Ala Leu Gln 245 250 255Arg Thr Val Pro Ala Ala Val Pro Gly Ile Val Phe Leu Ser Gly Gly 260 265 270Gln Ser Glu Glu Glu Ala Ser Val Asn Leu Asn Ala Ile Asn Gln Tyr 275 280 285Gln Gly Lys Lys Pro Trp Ala Leu Ser Phe Ser Tyr Gly Arg Ala Leu 290 295 300Gln Ala Ser Ala Leu Arg Ala Trp Gln Gly Lys Pro Glu Asn Ile Gly305 310 315 320Ala Gly Gln Lys Glu Leu Leu Gln Arg Ala Lys Ala Asn Val Leu Ala 325 330 335His Lys Gly Gln Tyr Val Ala Gly Ser Ile Pro Ser Leu Ala Ser Ala 340 345 350Lys Ser Asn Phe Val Ala Gln His Lys Tyr 355 360292429PRTDermatophagoides farinaemisc_feature(172)..(172)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(274)..(274)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(282)..(282)Xaa is serine, alanine, or 2-aminobutyric acid 292Ile Glu Gln Val His Ile Ser Leu Gly Thr Asn Ala Thr Glu Met Ile1 5 10 15Val Thr Trp Thr Glu Pro Gln Lys His Thr Asp Ile Asp Ile Asp Ala 20 25 30Val Val Tyr Tyr Gly Arg Ala Ser Ser Ser Phe Asp Gln Ala Ala Ile 35 40 45Ala Lys Ser Glu His Phe Lys Asp Asp Glu Thr Lys Tyr Thr Thr Phe 50 55 60Arg Ala Leu Leu Thr Gly Leu Glu Ser Asp Thr Arg Tyr His Tyr Lys65 70 75 80Ile Gln Leu Asp Asp Lys Glu Ser Ser Ile Phe Ala Phe Lys Thr Leu 85 90 95Lys Leu Asp Glu Asn Trp Leu Pro Arg Phe Ala Ile Tyr Gly Asp Leu 100 105 110Gly Tyr Val Asn Glu Gln Ser Leu Pro Tyr Leu Lys Lys Asp Val Glu 115 120 125Lys Asn Met Phe Asp Val Ile Phe His Ile Gly Asp Ile Ala Tyr Asp 130 135 140Leu Gln Asp Glu Asn Gly Glu Val Gly Asn Asn Phe Met Arg Ser Ile145 150 155 160Glu Ser Ile Ala Ser Lys Ile Pro Tyr Met Thr Xaa Pro Gly Asn His 165 170 175Glu Arg His Ser Asn Phe Ser His Tyr Asp Ser Arg Phe Ser Met Ile 180 185 190Gly Asp Arg Ser Gln Pro Asn His Gln Asp Ser Leu Asp Lys Arg Ile 195 200 205Asn Asn His Phe His Ser Met Glu Ile Gly Pro Ala Thr Ile Ile Met 210 215 220Phe Ser Thr Glu Tyr Tyr Tyr Tyr Thr Tyr Tyr Gly Trp Glu Gln Ile225 230 235 240Glu Arg Gln Tyr Arg Phe Leu Glu Lys Glu Leu Ile Arg Ala Asn Glu 245 250 255Asn Arg Asn Lys Arg Pro Trp Ile Ile Ala Met Gly His Arg Pro Leu 260 265 270Tyr Xaa Leu Lys Met Gly Asp Ser Ser Xaa Asp His Gln Thr Met Glu 275 280 285Arg Pro Glu Ile Arg Gln Gly Ile Arg Met His Asp Gln Gly Glu Arg 290 295 300Gln Tyr Gly Leu Glu Asp Leu Phe His Lys Tyr Gly Val Asp Ile Gln305 310 315 320Phe Tyr Gly His Glu His Phe Tyr Ala Arg Met Phe Pro Ile Tyr Lys 325 330 335Tyr Gln Met Tyr Lys Gly Lys Gln Ser Asp Asn Pro Tyr Asp His Ala 340 345 350Asp Gly Pro Ile His Ile Thr Thr Gly Ser Ala Gly Asn Lys Glu Ile 355 360 365His Pro Leu Phe Asn His Leu Lys Glu Trp Val Ala His His Phe Tyr 370 375 380Asp Tyr Gly Tyr Thr Arg Leu Ile Phe Glu Asn Gln Tyr Arg Ile Arg385 390 395 400Leu Gln Gln Val Ser Asp Asp Gln His Gly Lys Val Leu Asp Glu Ile 405 410 415Glu Ile Ile Lys Ser Ser Pro Gln Pro His Trp Met Pro 420 425293434PRTDermatophagoides pteronyssinusmisc_feature(173)..(173)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(275)..(275)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(283)..(283)Xaa is serine, alanine, or 2-aminobutyric acid 293Ile Glu Gln Val His Ile Ala Leu Gly Ser Asn Glu Thr Glu Ile Ile1 5 10 15Val Thr Trp Thr Glu Pro His Lys His Asp Asp Lys Thr Ser Asp Ala 20 25 30Val Val Tyr Tyr Gly Gln Ala Lys Ser Ser Phe Asp Gln Lys Val Lys 35 40 45Ala Ile Ser Glu Tyr Phe Lys Asp Asp Lys Thr Lys Tyr Thr Thr Tyr 50 55 60Arg Ala Leu Leu Thr Gly Leu Leu Pro Gly Thr Glu Tyr His Tyr Arg65 70 75 80Ile Gln Met Asp Asp Leu Glu Ser Ser Ile Phe Glu Phe Lys Thr Leu 85 90 95Lys Thr Gly Glu Glu Asn Trp Leu Pro Arg Phe Ala Ile Tyr Gly Asp 100 105 110Leu Gly Tyr Val Asn Glu Gln Ser Leu Pro Tyr Leu Lys Lys Asp Val 115 120 125Glu Gln Asn Leu Phe Asp Val Ile Phe His Ile Gly Asp Phe Ala Tyr 130 135 140Asp Leu Asn Asp Glu His Gly Lys Val Gly His His Phe Met Arg Ser145 150 155 160Ile Glu Pro Val Ala Ser Lys Val Ala Tyr Met Thr Xaa Pro Gly Asn 165 170 175His Glu Arg His Asp Asn Phe Ser His Tyr Asp Ser Arg Phe Ser Met 180 185 190Ile Gly Asp Arg Ser Gln Pro Ile His Ser Asp Lys Leu Asn Lys Arg 195 200 205Leu Asn Asn His Phe His Ser Met Thr Ile Gly Pro Ala Thr Ile Ile 210 215 220Leu Phe Ser Thr Glu Tyr Tyr Tyr Tyr Thr Lys Tyr Gly Trp Gln Gln225 230 235 240Ile Glu His Gln Tyr Arg Trp Leu Glu Gln Glu Leu Lys Arg Ala Asn 245 250 255Glu Asn Arg Gln Lys His Pro Trp Ile Ile Val Met Gly His Arg Pro 260 265 270Leu Tyr Xaa Leu Lys Met Gly Asp Asp Ser Xaa Asp His Gln Thr Met 275 280 285Glu Arg Lys Glu Ile Arg Gln Gly Ile Arg Met His Asp Glu Gly Glu 290 295 300Arg Gln Tyr Gly Leu Glu Asp Leu Phe Phe Lys Tyr Gly Val Asp Ile305 310 315 320Gln Phe Tyr Gly His Glu His Phe Tyr Ala Arg Leu Phe Pro Ile Tyr 325 330 335Lys Tyr Lys Met Tyr Asn Gly Thr Lys Ser Lys Asn Pro Tyr Asp His 340 345 350Pro Gly Ala Pro Ile His Ile Thr Thr Gly Ser Ala Gly Asn Lys Glu 355 360 365Leu His Pro Glu Phe Asn His Leu Asn Asp Trp Val Ala Glu His Phe 370 375 380Tyr Asp Tyr Gly Tyr Thr Arg Leu Met Phe Glu Asp Lys Tyr Arg Ile385 390 395 400Arg Leu Gln Gln Ile Ser Asp Asp Gln His Gly Lys Val Leu Asp Glu 405 410 415Ile Glu Ile Val Lys Ser Ser Pro Gln Pro His Trp Met Asn Val Glu 420 425 430His His294462PRTDermatophagoides farinaemisc_feature(15)..(15)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(374)..(374)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(442)..(442)Xaa is serine, alanine, or 2-aminobutyric acid 294Asp Ser Asn Ser Asp Thr Thr Phe Ile Phe Asn Gly Asp Gly Xaa Glu1 5 10 15Gln Asn His Leu Phe Gln Thr Arg Tyr Arg Pro Gln Ile Gln Gln Leu 20 25 30Ala Ser Asp Val Gln Arg Ile Ile Asp His Val Met Ser Val Asn Glu 35 40 45Ser Gly Arg Thr Tyr Arg Gln Leu Ala Glu Phe Val Asp Arg Phe Gly 50 55 60Ser Arg Leu Thr Gly Thr Lys Asn Leu Glu Asp Ser Ile Asp Tyr Met65 70 75

80Ile Asp Leu Leu Arg Gln Glu Gly His Asp Asn Val His Gly Glu Ser 85 90 95Val Gln Val Pro Arg Trp Thr Arg Gly Asn Glu Trp Ala Arg Met Ile 100 105 110Lys Pro Arg Glu Lys Lys Leu Asn Ile Leu Gly Leu Gly Tyr Ser Glu 115 120 125Gly Thr Asn Gly Gln Thr Ile Glu Ala Pro Ile Val Val Val Arg Asn 130 135 140Phe Thr Glu Leu Glu Gln Lys Ser Arg Leu Ile Pro Gly Lys Ile Val145 150 155 160Val Tyr Asn Phe His Tyr Glu Ser Tyr Gly Lys Gln Ala Ile Tyr Arg 165 170 175His Ser Gly Ala Ser Arg Ala Ala Glu Phe Gly Ala Val Ala Ala Met 180 185 190Ile Arg Ser Leu Thr Pro Phe Ser Ile Asp Ser Pro His Thr Gly Met 195 200 205Gln Thr Tyr Asp Val Asn Val Thr Arg Ile Pro Ala Ile Ser Ile Thr 210 215 220Ala Glu Asp Ala Asp Leu Phe Gln Arg Phe Ser Asp Arg Asn Glu Glu225 230 235 240Val Ile Val Gln Ile Tyr Ser Glu Asn Arg Asn Glu Lys Glu Gln Gly 245 250 255Ile Ser Arg Asn Thr Val Ser Asp Ile Arg Gly Glu Gln Tyr Pro Asp 260 265 270Glu Ile Val Leu Val Ser Gly His Ile Asp Ser Trp Asp Val Gly Gln 275 280 285Gly Ala Leu Asp Asp Gly Ala Gly Ser Phe Ile Ser Trp Arg Ala Leu 290 295 300Ser Val Ile Lys Gln Leu Gly Leu Arg Pro Lys Arg Thr Met Arg Ser305 310 315 320Ile Leu Trp Thr Gly Glu Glu Phe Gly Leu Ile Gly Val Tyr Asp Tyr 325 330 335Val Lys Lys His Gln Asn Glu Leu Lys Asn Tyr Val Leu Ala Met Glu 340 345 350Ser Asp Ile Gly Thr Phe Thr Pro Lys Gly Ile Thr Phe Ser Gly Arg 355 360 365Asn Ser Thr Ser Gln Xaa Thr Leu Trp Glu Ile Leu Gln Leu Met His 370 375 380Pro Ile Asn Ala Thr Thr Leu Thr Ile Ser Thr Glu Gly Ser Asp Val385 390 395 400Gln Ala Phe Tyr Glu Asn Gly Val Pro Ile Ser Ser Leu Asp Thr Ala 405 410 415Asn Asp Lys Tyr Phe Tyr Phe His His Thr Gln Gly Asp Thr Met Thr 420 425 430Val Glu Gln Ser Asp Asp Leu Asp Lys Xaa Gln Ala Leu Trp Thr Ser 435 440 445Ile Ser Tyr Ala Leu Ala Met Leu Asp Asp Arg Leu Pro Arg 450 455 460295462PRTDermatophagoides pteronyssinusmisc_feature(15)..(15)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(374)..(374)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(442)..(442)Xaa is serine, alanine, or 2-aminobutyric acid 295Asp Ser Asn Pro Gly Glu Thr Ser Ile Phe Asn Gly Glu Gly Xaa Ala1 5 10 15Asn Asp Gln Leu Phe Gln Thr Arg Ile Arg Pro Gln Ile Gln Gln Leu 20 25 30Ala Ser Asn Val Gln Arg Ile Ile Asp His Val Met Ser Ala Asn Glu 35 40 45Ser Gly Arg Thr Tyr Arg Gln Leu Ala Glu Phe Val Asp Arg Phe Gly 50 55 60Ser Arg Leu Thr Gly Thr Lys Asn Leu Glu Asp Ser Ile Asp Tyr Met65 70 75 80Ile Asp Leu Leu Lys Gln Glu Gly His Asp Asn Val His Gly Glu Pro 85 90 95Val Gln Val Pro Lys Trp Thr Arg Gly Asn Glu Trp Ala Arg Met Ile 100 105 110Lys Pro Arg Asp Lys Lys Leu Asn Ile Leu Gly Leu Gly Tyr Ser Glu 115 120 125Gly Thr Asn Gly Gln Thr Ile Glu Ala Pro Ile Val Val Val Arg Asn 130 135 140Phe Thr Glu Leu Glu Gln Lys Ala Gly Leu Ile Pro Gly Lys Ile Val145 150 155 160Val Tyr Asn Phe Lys Tyr Glu Ser Tyr Gly Lys Gln Ala Ile Tyr Arg 165 170 175His Ser Gly Ala Ser Arg Ala Ala Lys Phe Gly Ala Val Ala Ala Met 180 185 190Ile Arg Ser Leu Thr Pro Phe Ser Ile Asp Ser Pro His Thr Gly Met 195 200 205Gln Ser Tyr Asp Val Asn Val Thr Lys Ile Pro Ala Ile Ser Ile Thr 210 215 220Thr Glu Asp Ala Asp Leu Phe Gln Arg Phe Ser Asp Arg Asn Glu Glu225 230 235 240Val Ile Val Gln Ile Tyr Ser Glu Asn His Asn Glu Lys Asp Lys Gly 245 250 255Ile Ser Arg Asn Thr Val Ser Asp Val Arg Gly Glu Lys Tyr Pro Asn 260 265 270Glu Ile Val Leu Val Ser Gly His Ile Asp Ser Trp Asp Val Gly Gln 275 280 285Gly Ala Ser Asp Asp Gly Ala Gly Ala Phe Ile Ser Trp Arg Ala Leu 290 295 300Ser Val Ile Lys Lys Leu Gly Leu Arg Pro Lys Arg Thr Leu Arg Ser305 310 315 320Val Leu Trp Thr Gly Glu Glu Phe Gly Leu Ile Gly Val Tyr Asp Tyr 325 330 335Ile Lys Lys His Arg Asn Glu Leu Lys Asp Tyr Val Ile Ala Met Glu 340 345 350Ser Asp Ile Gly Thr Phe Thr Pro Arg Gly Ile Thr Tyr Ser Gly Lys 355 360 365Asn Ser Thr Ser Gln Xaa Thr Leu Trp Glu Ile Leu Gln Leu Met His 370 375 380Pro Ile Asn Ala Thr Thr Leu Thr Ile Ser Thr Glu Gly Ser Asp Val385 390 395 400Gln Ala Phe Tyr Glu Asn Gly Val Pro Ile Ser Ser Leu Asp Thr Ala 405 410 415Asn Asp Lys Tyr Phe Tyr Phe His His Thr Gln Gly Asp Thr Met Thr 420 425 430Val Glu Gln Pro Asp Asp Leu Asp Lys Xaa Gln Ala Leu Trp Thr Ser 435 440 445Val Ser Tyr Ala Leu Ala Met Leu Asp Asp Arg Leu Ser Arg 450 455 460296463PRTDermatophagoides farinaemisc_feature(6)..(6)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(30)..(30)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(96)..(96)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(114)..(114)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(243)..(243)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(246)..(246)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(279)..(279)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(286)..(286)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(309)..(309)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(319)..(319)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(329)..(329)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(348)..(348)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(449)..(449)Xaa is serine, alanine, or 2-aminobutyric acid 296Asp Thr Pro Ala Asn Xaa Thr Tyr Glu Asp Ile Lys Gly Leu Trp Leu1 5 10 15Phe Glu Glu Ser Thr Pro Ile Asn Asp Arg Thr Glu Lys Xaa Asp Asn 20 25 30Gly Arg Arg Glu Tyr Thr Lys Lys Ile Tyr Val Arg Leu Asp Phe Pro 35 40 45Asn Thr Ala Val Asp Lys Phe Gly Asn Val Gly Thr Trp Thr Leu Ile 50 55 60Tyr Asn Gln Gly Phe Glu Val Ile Ile Asn Tyr Arg Lys Tyr Phe Ala65 70 75 80Phe Ser Ala Tyr Glu Arg Lys Ser Asn Ser Lys Val Ile Ser Tyr Xaa 85 90 95His Lys Thr Ile Pro Gly Trp Ser His Asp Leu Leu Gly Asn Asn Trp 100 105 110Ala Xaa Tyr Ile Gly His Lys Val Asn Asp Trp Asn Ser Ser Pro Leu 115 120 125Gln Lys Ile Gly Ser Glu Gln Phe Pro Ile Lys Glu His Ile Glu Gln 130 135 140Pro Leu Tyr Leu Lys Asn Ile Asp Leu Ser His Ala Leu Ser Gln Asn145 150 155 160His Val Asp Gln Ile Asn Ser Lys Gln Lys Ser Trp Lys Ala Thr Val 165 170 175Tyr Pro Glu Met Gln Ser Lys Thr Val Glu His Leu Ile Lys Met Ala 180 185 190Gly Gly Glu Lys Ser Arg Ile Met Ser Arg Pro Lys Pro Ile Arg Ala 195 200 205Thr Glu Gln Gln Arg His Glu Ala Arg Gly Leu Pro Glu Ser Phe Asp 210 215 220Trp Arg Asn Val Asp Gly Ile Asn Tyr Val Ser Pro Val Arg Asn Gln225 230 235 240Gly Asn Xaa Gly Ser Xaa Tyr Ala Phe Ala Ser Met Ala Met Leu Glu 245 250 255Ala Arg Ile Arg Ile Ala Thr Asn Asn Thr Ala Lys Pro Val Phe Ser 260 265 270Pro Gln Glu Val Val Asp Xaa Ser Glu Tyr Ser Gln Gly Xaa Asp Gly 275 280 285Gly Phe Gly Tyr Leu Ile Ala Gly Lys Tyr Ala Gln Asp Phe Gly Val 290 295 300Val Glu Glu Ser Xaa Tyr Pro Tyr Lys Ala Tyr Thr Gly Lys Xaa Lys305 310 315 320Leu Asp Tyr Asn Thr Thr Ala Lys Xaa Gln Gln Arg Thr Tyr Thr Ile 325 330 335Lys Tyr Asn Tyr Leu Gly Gly Tyr Phe Gly Ala Xaa Asn Glu Glu Ala 340 345 350Met Arg Ile Glu Leu Val Lys Asn Gly Pro Ile Ala Val Gly Phe Glu 355 360 365Val Tyr Lys Asp Phe Met Thr Tyr Arg Arg Gly Ile Tyr Ser His Asp 370 375 380Ser Asp Tyr Glu Thr Glu Gln Lys Val Gly Val Glu Phe Asn Pro Phe385 390 395 400Val Leu Thr Asn His Ala Val Leu Ile Val Gly Tyr Gly Arg Asp Glu 405 410 415Lys Ser Gly Glu Asn Tyr Trp Ile Val Lys Asn Ser Trp Gly Glu Gln 420 425 430Trp Gly Ile Asp Gly Gly Tyr Phe Leu Ile Arg Arg Gly Thr Asn Glu 435 440 445Xaa Gly Ile Glu Ser Ile Ala Met Ala Ala Thr Pro Ile Pro Asn 450 455 460297474PRTDermatophagoides pteronyssinusmisc_feature(6)..(6)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(30)..(30)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(99)..(99)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(117)..(117)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(249)..(249)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(252)..(252)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(285)..(285)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(292)..(292)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(315)..(315)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(325)..(325)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(338)..(338)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(357)..(357)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(460)..(460)Xaa is serine, alanine, or 2-aminobutyric acid 297Asp Thr Pro Ala Asn Xaa Thr Tyr Glu Asp Ile Lys Gly Leu Trp Leu1 5 10 15Phe Glu Glu Thr Glu Pro Ile Lys Asp Arg Trp Glu Lys Xaa Pro Glu 20 25 30His Gln Gln Gln Arg Glu Lys Tyr Ser Lys Lys Ile Phe Ile Arg Leu 35 40 45Asp Phe Pro Asn Val Ala Val Asp Lys Phe Gly Asn Ile Gly Glu Trp 50 55 60Thr Met Ile Tyr Asn Gln Gly Phe Glu Val Lys Ile Asn Tyr Arg Lys65 70 75 80Tyr Phe Ala Phe Ser Ala Tyr Glu Arg Lys Ser Glu Asn Asn Val Leu 85 90 95Ser Tyr Xaa His Lys Thr Gln Pro Gly Trp Ser His Asp Val Leu Gly 100 105 110Asn Asn Trp Ala Xaa Tyr Val Gly His Lys Val Asn Asn Trp Asn Asp 115 120 125Asp Asp Val Ser Lys Thr Thr Thr Val Gly Ala Glu Lys Phe Pro Val 130 135 140Lys Gln His Ser Glu Arg Glu Leu Tyr Leu Gln Asn Ile Asn Val Glu145 150 155 160His Ile Leu Ser Gln Lys His Ile Asp His Leu Asn Ser Gln Gln Lys 165 170 175Ser Trp Lys Ala Ile Val Tyr Pro Asp Leu Gln Ser Lys Ser Ile Glu 180 185 190His Leu Ile Gln Met Ala Gly Gly Arg Lys Ser Arg Ile Ile Asn Arg 195 200 205Pro Lys Pro Leu Arg Ala Thr Glu Gln Gln Lys Gln Leu Ala Arg Ser 210 215 220Leu Pro Glu Ser Phe Asp Trp Arg Asn Leu Asn Gly Ile Asp Tyr Val225 230 235 240Ser Pro Val Arg Asp Gln Gly Lys Xaa Gly Ser Xaa Tyr Thr Phe Ala 245 250 255Ser Met Ala Met Leu Glu Ser Arg Ile Arg Ile Gln Thr Asn Asn Thr 260 265 270Phe Lys Pro Ile Phe Ser Thr Gln Glu Val Val Asp Xaa Ser Glu Tyr 275 280 285Ser Gln Gly Xaa Asp Gly Gly Phe Ser Tyr Leu Ile Ala Gly Lys Tyr 290 295 300Ala Gln Asp Phe Gly Val Ile Asp Glu Ser Xaa Tyr Pro Tyr Lys Gly305 310 315 320Val Thr Gly Lys Xaa Gln Asn Gln Gln Asn Phe Asn Gln Thr Asn Glu 325 330 335Lys Xaa Lys Gln Arg Thr Tyr Thr Ile Asp Tyr Lys Tyr Val Gly Gly 340 345 350Tyr Phe Gly Ala Xaa Asn Glu Glu Ala Met Gln Ile Glu Leu Val Gln 355 360 365Asn Gly Pro Ile Ala Val Gly Phe Glu Val Tyr Gly Asp Phe Phe Gly 370 375 380Tyr Ser Glu Gly Ile Tyr Ser His Gln Pro Ser Asn Glu Ser Asn Asp385 390 395 400Gln His Gln Gln Ile Lys Ala Glu Phe Asn Pro Phe Glu Met Thr Asn 405 410 415His Ala Val Leu Ile Val Gly Tyr Gly Lys Asp Lys Lys Thr Gly Glu 420 425 430Lys Tyr Trp Ile Val Lys Asn Ser Trp Gly Lys Gln Trp Gly Met Asp 435 440 445Gly Tyr Phe Trp Met Arg Arg Gly Thr Asp Glu Xaa Ala Ile Glu Ser 450 455 460Leu Ala Met Ala Ala Thr Pro Ile Pro Asn465 470298509PRTDermatophagoides farinaemisc_feature(14)..(14)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(39)..(39)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(310)..(310)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(374)..(374)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(462)..(462)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(480)..(480)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(494)..(494)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(507)..(507)Xaa is serine, alanine, or 2-aminobutyric acid 298Gln Ser Arg Asp Arg Asn Asp Lys Pro Tyr Arg Ile Val Xaa Tyr Trp1 5 10 15Gly Thr Trp Ala Phe Tyr Arg Pro Ala Ser Gly Lys Phe Gln Ala Glu 20 25 30Asn Val Asn Pro Asn Leu Xaa Thr His Ile Met Tyr Gly Phe Ala Lys 35 40 45Leu Gln Asn Asn Lys Ile Ala Leu Tyr Asp Pro Asp Leu Asp Asp Gly 50 55 60Asp Glu Asp Trp Asn Ser Gly Leu Gln Trp Gly His Gly Met Ile Arg65 70 75 80Arg Met Val Asn Leu Arg Thr Tyr Asn Pro His Leu Thr Thr Met Ile 85 90 95Ser Leu Gly Gly Trp Asn Glu Gly Ser Asp Lys Tyr Ser Ile Met Val 100 105 110Arg Asp Pro Ala Ser Arg Lys Ile Phe Ile Gln Ser Val Leu His Leu 115 120 125Leu Ala Glu Phe Asp Leu Asp Gly Leu Asp Phe Asp Trp Glu Tyr Pro 130 135 140Ala Met Gln Ala Ser Gly Asp Ser Asp Arg Lys Pro Gly Arg Ala Glu145 150 155 160Asp Lys Glu Asp Phe Val Thr Leu Leu Arg Glu Leu His Glu Ala Phe 165 170 175Gln Pro His Gly Tyr Val Leu Ser Ser Ala Val Ser Ala Gly Lys Pro 180 185 190Thr Ile Asp Arg Ala Tyr Asn Ile Pro Glu Val Ser Lys Tyr Leu Asp 195 200 205Phe Ile Asn Leu Met Ser Tyr Asp Tyr His Gly Gly Trp Glu Ser His 210 215 220Thr Gly His Asn Ala Pro Leu Asn Ser Tyr Lys Asn Ala Asn Glu Leu225 230 235 240Asp Lys Glu Phe Thr Val Thr Tyr Ser Val Glu Tyr Trp Leu Asn His 245 250 255Gly Val Asp Pro Lys Lys Leu Val Leu Gly Ile Pro Leu Tyr Gly Arg 260 265 270Thr Phe Thr Leu Ala Gly Ser Glu His Gly Ile Gly Ala Pro Thr Ile 275 280 285Gly Lys Gly Gly Glu Ser Gly Thr Ile Thr Arg Thr Ile Gly Met Leu 290 295 300Gly Tyr Asn

Glu Ile Xaa Thr Met Ile Lys Gln Gly Trp Gln Leu Tyr305 310 315 320Arg Asp Glu Ile Glu Arg Ile Pro Tyr Ala Val His Ala Asn Gln Trp 325 330 335Ile Gly Tyr Asp Asp Arg Glu Ser Val Asn Glu Lys Leu Asn Leu Leu 340 345 350Met Ala Lys His Leu Gly Gly Ala Met Val Trp Ser Ile Asp Thr Asp 355 360 365Asp Phe Val Gly Asn Xaa Val Gly Val Lys Tyr Pro Leu Leu Arg Ser 370 375 380Ile Ser Lys Lys Leu Asn Asn Val Asp Gly Pro Asp Pro Asp Ile Lys385 390 395 400Arg Tyr His Tyr His Thr Ser Thr Ala Lys Pro His Thr Asp Gly Thr 405 410 415Thr Ser Thr His His Asp His Lys Thr Thr Thr Thr Lys His His Lys 420 425 430Thr Thr Gln Pro His His Lys Thr Thr Gln Pro His His Thr Gln Thr 435 440 445Ile Thr Thr Thr Thr Glu Arg Pro His Gly Lys Phe Gln Xaa His Gln 450 455 460Ala Gly Phe Phe Ala Asp Pro Glu Asn Pro Arg Lys Phe His Gln Xaa465 470 475 480Val Asp Phe Gly Gly His Leu Lys Asp Tyr Glu Phe Met Xaa Gly Glu 485 490 495Gly Thr His Tyr Asp Glu Lys Leu His Ile Xaa Val Arg 500 505299520PRTDermatophagoides farinaemisc_feature(7)..(7)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(85)..(85)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(98)..(98)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(117)..(117)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(129)..(129)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(187)..(187)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(292)..(292)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(338)..(338)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(343)..(344)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(400)..(400)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(405)..(405)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(419)..(419)Xaa is serine, alanine, or 2-aminobutyric acid 299Lys Lys Ala Pro Glu Gly Xaa Phe Arg Ala Ala Val Leu Asp His Val1 5 10 15His Gln Thr Asn Val Arg Gln Leu Ser Asp Phe Ala Lys Ile Ile Glu 20 25 30Leu Asn Phe Lys Val Tyr Glu Asp Ala Ala Ala Leu Ala Lys Lys Gln 35 40 45Gly Ala Asp Ile Ile Val Phe Pro Glu Asp Gly Leu Ile Tyr Asn Ile 50 55 60Ala Ser Arg Glu Lys Ala Asp Glu Phe Ala Ser Asp Ile Pro Asp Gly65 70 75 80Glu Thr Asn Ala Xaa Thr Leu Glu Thr Lys Ser Val Tyr Asn Arg Leu 85 90 95Ala Xaa Leu Ala Gln Lys His Glu Ile Phe Val Val Ala Asp Leu Ile 100 105 110Asp Arg Lys Ser Xaa Glu Glu Leu Gly Ile Ser Asn Thr Ser Asp Ser 115 120 125Xaa Pro Ala Asp Lys Lys Phe Leu Phe Asn Thr Ala Val Leu Phe Asp 130 135 140Arg Gln Gly Lys Leu Leu Gly Arg Tyr His Lys Met His Leu Phe Gly145 150 155 160Glu Met Thr Met Asn Ile Pro Pro Lys Pro Glu Leu Leu Val Ile Asp 165 170 175Thr Glu Leu Gly Arg Leu Gly Met Gln Ile Xaa Phe Asp Met Ile Phe 180 185 190Lys Thr Pro Gly His Phe Leu Ala Glu Gln Asn Lys Phe Asp Thr Met 195 200 205Leu Phe Pro Thr Trp Trp Phe Asp Glu Ala Pro Met Leu Ser Ser Ser 210 215 220Gln Tyr Gln Met Ala Trp Ala Phe Gly Asn Asn Val Thr Leu Leu Ala225 230 235 240Ser Asn Ile His Arg Val Glu Leu Gly Ser Arg Gly Ser Gly Ile Tyr 245 250 255Val Gly Pro His Gln Thr Leu Ala Thr Ala Leu Tyr Asp Asp Ser Val 260 265 270Glu Arg Leu Val Leu Ala Asn Val Pro Ile Lys Pro Arg Glu Thr Asp 275 280 285Lys Ser Val Xaa Pro Leu Asp Ser Glu Ile Ile Glu Val Pro Gln Gln 290 295 300Ile Pro Ile Pro Asn Ser Val Lys Tyr His His Leu Asn Met Asn Leu305 310 315 320Leu Asp Val Thr Leu Val Glu Leu Ser Ser Lys Asp Ser Glu Phe His 325 330 335Ile Xaa Tyr Lys Gly Val Xaa Xaa Gln Ile Glu Tyr Arg Leu Ala Val 340 345 350Lys Asp Gln Pro Arg Glu Ser Trp Val Asp Arg Val Pro Leu Leu Ala 355 360 365Asn Met Leu Glu Tyr Phe Thr Pro Glu Glu Arg Tyr Tyr Leu Met Val 370 375 380Ala Asn Arg Thr Arg Pro Gly Thr Tyr Arg Trp Thr Glu Glu Ile Xaa385 390 395 400Ala Val Val Val Xaa Pro Ser Ser Arg Trp Asn Ile Gly Lys Val Glu 405 410 415Lys Asp Xaa Ser Gln Phe Gly Ser Asn Gln Glu Leu Asn Ser Arg Phe 420 425 430Val Tyr Ala Lys Leu Arg Gly Ala Phe Ser Glu Ser Thr Ala Val Tyr 435 440 445Pro Ser Ala Val Gly Pro Lys Asn Gln Leu Ile Asn Pro Glu Asn Lys 450 455 460Trp Lys Tyr Trp Lys Val Asn Val Pro Asp Lys Pro Glu His Phe Val465 470 475 480Glu Leu Gly Ala Lys Asp Asn Pro Glu Ser Lys Ala Ile Glu Leu Ser 485 490 495Thr Leu Ala Leu Tyr Gly Arg Asn Tyr Asp Leu Asp Pro Thr Tyr Lys 500 505 510Gln Lys Pro Val Pro Ile Asn Leu 515 520300519PRTDermatophagoides pteronyssinusmisc_feature(7)..(7)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(85)..(85)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(98)..(98)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(117)..(117)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(129)..(129)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(187)..(187)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(292)..(292)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(338)..(338)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(343)..(344)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(400)..(400)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(405)..(405)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(419)..(419)Xaa is serine, alanine, or 2-aminobutyric acid 300Lys Ser Ala Pro Glu Gly Xaa Phe Arg Ala Ala Val Leu Asp His Val1 5 10 15His Gln Thr Asp Ala Arg His Leu Ser Asn Thr Ala Lys Ile Ile Asp 20 25 30Leu Asn Phe Lys Val Tyr Glu Asp Ala Ala Ala Leu Ala Lys Lys Gln 35 40 45Gly Ala Asp Ile Ile Val Phe Pro Glu Asn Gly Leu Ile Tyr Ser Ile 50 55 60Leu Ser Arg Glu Lys Ala Asp Glu Phe Ala Ser Asp Ile Pro Asp Ala65 70 75 80Glu Val Asn Ala Xaa Thr Leu Asp Ser Lys Phe Val Tyr Asn Arg Leu 85 90 95Ala Xaa Leu Ala Gln Lys His Gln Met Phe Val Val Ala Asp Leu Ile 100 105 110Asp Arg Lys Ser Xaa Glu Glu Leu Gly Ile Asn Asn Val Ser Asp Ser 115 120 125Xaa Pro Ala Asp Lys Lys Phe Leu Phe Asn Thr Ala Val Leu Phe Asp 130 135 140Arg Gln Gly Lys Leu Leu Gly Arg Tyr His Lys Met His Leu Phe Gly145 150 155 160Glu Ile Ser Met Asn Pro Pro Pro Lys Pro Glu Leu Leu Val Ile Asp 165 170 175Thr Glu Leu Gly Arg Leu Gly Met Gln Ile Xaa Phe Asp Met Ile Phe 180 185 190Lys Thr Pro Gly Tyr Leu Leu Ala Gln Glu Asn Lys Phe Asp Thr Met 195 200 205Leu Phe Pro Thr Trp Trp Phe Asp Glu Ser Pro Met Leu Ser Ser Ser 210 215 220Gln Tyr Gln Met Ala Trp Ala Phe Gly Asn Asn Val Thr Leu Leu Ala225 230 235 240Ser Asn Ile His Arg Ile Glu Val Gly Ser Arg Gly Ser Gly Ile Tyr 245 250 255Val Gly Pro His Arg Thr Leu Ala Ala Ala Leu Tyr Asp Asp Ser Val 260 265 270Glu Arg Leu Val Leu Ala Asn Val Pro Ile Lys Pro Lys Glu Thr Asp 275 280 285Gln Ser Ala Xaa Pro Leu Asp Ser Glu Ile Ile Glu Val Pro Gln Gln 290 295 300Ile Pro Ile Pro Lys Ser Val Lys Tyr His His Gln Asn Leu Asn Leu305 310 315 320Lys Asp Val Thr Leu Leu Gln Leu Ser Ser Asn Glu Ser Glu Val His 325 330 335Leu Xaa His Lys Gly Val Xaa Xaa Gln Phe Glu Tyr Arg Leu Ala Met 340 345 350Lys Asp Gln Pro Gln Glu Ser Trp Val Asp Arg Val Pro Leu Leu Ala 355 360 365Asn Met Leu His Tyr Leu Thr Pro Glu Glu Arg Tyr Tyr Leu Leu Ile 370 375 380Ala Asn Arg Thr Arg Pro Gly Ala Tyr Pro Trp Ser Glu Glu Phe Xaa385 390 395 400Ala Val Val Val Xaa Pro Ser Ser Arg Trp Asn Phe Gly Lys Met Gln 405 410 415Lys Asp Xaa Ser Lys Ile Gly Ser Asn Gln Glu Leu Ser Ser Arg Phe 420 425 430Val His Ala Lys Leu Arg Gly Lys Phe Ser Glu Asp Thr Ala Val Tyr 435 440 445Pro Ser Ala Val Gly Ser Lys Asn Gln Leu Ile Tyr Pro Glu Asn Lys 450 455 460Trp Lys Phe Trp Lys Val Asn Val Pro Asn Glu Pro Glu Tyr Phe Ile465 470 475 480Glu Leu Gly Ala Lys Asp Asn Ser Glu Ser Arg Ala Met Glu Leu Gly 485 490 495Ala Leu Val Leu Tyr Gly Arg Asn Tyr Asn Arg Asp Pro Arg Tyr Glu 500 505 510Gln Lys Ala Leu Pro Ile Asn 515301887PRTDermatophagoides pteronyssinusmisc_feature(8)..(8)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(19)..(19)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(30)..(30)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(35)..(36)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(61)..(61)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(311)..(311)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(382)..(382)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(472)..(472)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(499)..(499)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(589)..(589)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(600)..(600)Xaa is serine, alanine, or 2-aminobutyric acid 301Leu Asp Ser Asp Pro Met Lys Xaa Asn Ser Ile Arg Asn Glu Asp Arg1 5 10 15Ile Asp Xaa Asn Pro Asp Pro Pro Ile Ser Lys Glu Ile Xaa Glu Gln 20 25 30Arg Gly Xaa Xaa Trp Asn Ala Gly Asn Asn Thr Asp Asp Gly Asn Leu 35 40 45Ile Ser Arg Ala Leu Pro His Leu Gly Val Pro Ser Xaa Tyr Tyr Gly 50 55 60Glu Asn Tyr Ile Gly Tyr Lys Ile Glu Lys Ile Tyr Ile Lys Asp Glu65 70 75 80Asp Leu Ser Met Thr Lys Leu Lys Arg Val Arg Pro Ser Gly Phe Pro 85 90 95Lys Asp Ile Glu Asn Val Asn Ile Glu Ile His Gln Leu Asn Asp Gln 100 105 110Val Leu Arg Leu Lys Phe Ile Asp Ala Asn Gln Lys Arg Tyr Glu Val 115 120 125Pro Thr Pro Lys Leu Asn Ile Pro Ser Val Ser Lys Ser Ser Asn Ser 130 135 140Arg Leu Tyr Ser Thr Glu Ile Ser Gly Ser His Leu Ile Val Arg Arg145 150 155 160Arg Glu Thr Asn Gln Ser Ile Phe Asp Ile Asn Leu Ala Gln Met Val 165 170 175Tyr Ser Asp Gln Leu Ile His Leu Thr Ser Lys Leu Pro Ser Lys Tyr 180 185 190Ile Tyr Gly Ile Gly Glu His Arg Glu Pro Phe Arg Lys Thr Thr Asp 195 200 205Trp Lys Arg Tyr Thr Gln Trp Thr Arg Asp Gln Val Pro Ile Ser Asp 210 215 220His Ala Leu Tyr Gly Ser His Pro Phe Tyr Met Met Val Glu Asn Lys225 230 235 240Thr Lys Leu Ala Ser Gly Val Phe Leu Phe Asn Ser Asn Ala Met Asp 245 250 255Ile Leu Thr Gln Pro Ser Pro Ala Ile Thr Phe Arg Thr Val Gly Gly 260 265 270Ile Leu Asp Phe Phe Ile Phe Phe Gly Pro Lys Pro Glu Gln Val Val 275 280 285Gln Gln Tyr His Asn Leu Ile Gly Leu Pro Ala Met Pro Pro Phe Trp 290 295 300Ser Leu Gly Tyr Gln Gln Xaa Arg Tyr Gly Tyr Asn Asn Phe Thr Asn305 310 315 320Leu Asn Gln Thr Tyr Trp Arg Thr Arg Gln Ala Gly Ile Pro Met Asp 325 330 335Val Gln Trp Thr Asp Ile Asp Met Phe Asp Ser Tyr Asn Asp Phe Thr 340 345 350Tyr Asn His Lys Gln Phe Lys Glu Leu Pro Asp Phe Ile Arg Asn Val 355 360 365Leu His Lys Asn Gly Gln Lys Phe Ile Pro Met Phe Asp Xaa Gly Ile 370 375 380Ser Ser Gly Glu Lys Ala His Ser Tyr Arg Pro Tyr Asp Tyr Gly Val385 390 395 400Glu Leu Asp Ile Phe Val Lys Asn Ser Ser Lys Gln Ile Phe Asn Gly 405 410 415Lys Val Trp Asn Gly Lys Ser Thr Val Trp Pro Asp Phe Ser His Pro 420 425 430Asn Ala Thr Lys Tyr Trp Ser Lys Met Phe Glu Glu Tyr His Lys Ile 435 440 445Ile Glu Phe Asp Gly Ala Trp Ile Asp Met Asn Glu Pro Ser Asn Phe 450 455 460Tyr Asp Gly Gln Ile Asp Gly Xaa Pro Lys Thr Glu Ile Glu Asn Pro465 470 475 480Gln Tyr Val Pro Gly Met Thr Asp Asp Ser Leu Thr Leu Arg His Lys 485 490 495Thr Leu Xaa Met Thr Ala Arg His Tyr Asn Asp Gln Leu His Tyr Asn 500 505 510Leu His Asn Leu Tyr Gly Phe Gln Glu Ala Ile Ala Thr Asn Glu Ala 515 520 525Leu Lys Thr Thr Leu Asn Lys Arg Pro Phe Ile Ile Ser Arg Ser Ser 530 535 540Ala Pro Gly His Gly His Trp Ala Ser His Trp Asp Gly Asp Val Ile545 550 555 560Ser Asp Trp Ser Ser Met Arg Trp Thr Ile Pro Ser Ile Leu Asn Phe 565 570 575Asn Leu Phe Gly Val Pro Met Ile Gly Ala Asp Ile Xaa Gly Phe Asn 580 585 590Gly Asp Thr Thr Val Glu Leu Xaa Arg Arg Trp Tyr Gln Leu Gly Ala 595 600 605Phe Tyr Ser Phe Val Arg Asn His Asn Thr Asp Asn Ala Ile Asp Gln 610 615 620Asp Pro Val Ala Leu Gly Glu Thr Val Val Arg Thr Ala Arg Ser Ala625 630 635 640Leu Thr Tyr Arg Tyr Ala Phe Leu Pro Tyr Leu Tyr Thr Leu Phe Tyr 645 650 655Asn Val His Gln Asn Gly Gly Thr Val Leu Arg Pro Met Phe Phe Glu 660 665 670Phe Pro Asp Asp Asp His Leu Tyr Asp Ile Glu Thr Gln Phe Met Trp 675 680 685Gly Asp Ser Met Leu Ile Ala Pro Ile Leu Tyr Pro Asn Gln Thr Glu 690 695 700Asn Lys Val Tyr Leu Pro Lys Gly Thr Trp His Asn Met Arg Gln Thr705 710 715 720Phe Glu Ser Gln Gly Gln Tyr Phe Thr Ile Lys Asp Ser Leu Asp Asp 725 730 735Ile Asn Tyr Val Phe Phe Arg Ser Gly Ser Ile Ile Pro Ile Gln Gly 740 745 750Pro Gln Asn Asn Thr Glu Met Met Lys Ser Lys Asp Phe Gly Leu Val 755 760 765Val Ile Leu Asp Ser Lys Asn Pro Glu Pro Tyr Ala Lys Gly Ser Leu 770 775 780Tyr Leu Asp Ser Gly Asp Ser Leu Asp Pro Val Lys Lys Gly Glu Tyr785 790 795 800Asn Phe Tyr Asn Phe Glu Val Lys Asn Asn Thr Leu Thr Ile Glu Ser 805 810 815Gln His Leu Gly Tyr Gln Thr Asn Gln Ser Ile Ile Ile Leu Glu Ile 820 825 830Leu Gly Ile Asp Arg Lys Pro Thr Ser Ile Ile Phe Asp Gly Lys Pro 835 840 845Tyr Tyr Gln Phe Ile Tyr Thr Thr Asn Asn Met Leu Ile Ile Gln Thr 850 855

860Lys Leu Ser Ile Phe Asn Asp Asn Asp Lys Ser Lys Lys Ile His Tyr865 870 875 880Gln Phe Glu Trp Lys Phe Asn 885302885PRTDermatophagoides farinaemisc_feature(5)..(5)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(16)..(16)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(27)..(27)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(32)..(33)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(57)..(57)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(306)..(306)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(377)..(377)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(467)..(467)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(494)..(494)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(583)..(583)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(594)..(594)Xaa is serine, alanine, or 2-aminobutyric acid 302Asp Ser Leu Lys Xaa Ser Ser Ile Arg Asn Glu Asp Arg Ile Asp Xaa1 5 10 15Asn Pro Asp Pro Pro Ile Ser Lys Asn Val Xaa Glu Gln Arg Gly Xaa 20 25 30Xaa Trp Lys Thr Ala Gly Asn Asp Leu Lys Asn Leu Ser Ser Lys Val 35 40 45Leu Pro Asn Leu Asn Val Pro Tyr Xaa Tyr Tyr Gly Glu Asn Tyr Ile 50 55 60Gly Tyr Lys Ile Glu Lys His Ser Lys Asn Leu Ile Gln Leu Lys Arg65 70 75 80Asn Arg Ser Ser Gly Phe Ala Arg Asp Ile Glu Asn Ile Asn Ile Glu 85 90 95Ile His Glu Leu Asn Asp Lys Val Ile Arg Leu Lys Phe Ile Asp Ala 100 105 110Asn Lys Lys Arg Tyr Glu Val Pro Ile Pro Lys Leu Asn Leu Pro Ser 115 120 125Thr Thr Ser Ser Ser Ser Ser Asn Ser Arg Leu Tyr Ser Val Glu Leu 130 135 140Asp Gly Ser His Leu Ile Val Arg Arg Arg Glu Thr Asn Gln Ser Ile145 150 155 160Phe Asp Ile Asn Leu Ala Tyr Met Val Tyr Ser Asp Gln Leu Ile His 165 170 175Val Thr Ser Arg Leu Pro Ser Lys Tyr Ile Tyr Gly Leu Gly Glu His 180 185 190Arg Ala Pro Phe Arg Lys Asn Thr Asn Trp Lys Arg Tyr Thr Gln Trp 195 200 205Thr Arg Asp Gln Tyr Pro Val Thr Asp Lys Ala Leu Tyr Gly Asn His 210 215 220Pro Phe Tyr Leu Thr Val Glu Asp Glu Ser Pro Lys Lys Ser Ala Ser225 230 235 240Gly Val Phe Leu Phe Asn Ser Asn Ala Met Asp Ile Ile Thr Gln Pro 245 250 255Ser Pro Ala Ile Thr Phe Arg Thr Ile Gly Gly Ile Leu Asp Phe Phe 260 265 270Val Phe Phe Gly Pro Lys Pro Glu Asp Val Ile Ser Gln Tyr Gln Asn 275 280 285Leu Ile Gly Leu Pro Ala Met Pro Pro Phe Trp Ser Leu Gly Tyr Gln 290 295 300Gln Xaa Arg Tyr Gly Tyr Asn Asn Phe Thr Asn Leu Asn Thr Thr Tyr305 310 315 320Thr Arg Asn Arg Ala Val Gly Ile Pro Met Asp Val Gln Trp Thr Asp 325 330 335Ile Asp Ala Phe Asn Ser Asn Asn Asp Phe Thr Tyr Asp His Lys Arg 340 345 350Phe Lys Glu Leu Pro Asp Phe Ile Asn Asn Val Leu His Pro Asn Gly 355 360 365Gln Lys Phe Ile Pro Met Phe Asp Xaa Gly Ile Ser Ser Gly Glu Pro 370 375 380Ala Gly Ser Tyr Lys Pro Phe Asp Ser Gly Val Glu Leu Asp Val Phe385 390 395 400Val Lys Asn Ser Ser Asn Lys Ile Phe Arg Gly Lys Val Trp Asn Gly 405 410 415Lys Ser Thr Val Trp Pro Asp Phe Ser His Pro Asn Ala Thr Glu Tyr 420 425 430Trp Met Asp Met Phe Ala Glu Tyr His Lys Thr Ile Ala Phe Asp Gly 435 440 445Ala Trp Leu Asp Met Asn Glu Pro Ser Asn Phe Tyr Asn Gly Glu Glu 450 455 460His Gly Xaa Pro Glu Ser Glu Ile Glu Asn Pro Gln Tyr Val Pro Gly465 470 475 480Met Thr Asp Asp Ser Leu Thr Leu Arg His Lys Thr Leu Xaa Met Thr 485 490 495Ala Arg His Tyr Asn Asp Gln Leu His Tyr Asn Leu His Asn Leu Tyr 500 505 510Ser Leu Ser Met Ala Met Ala Thr Asn Ala Ala Leu Thr Lys Leu Asn 515 520 525Lys Arg Pro Phe Ile Ile Ser Arg Ala Thr Ala Pro Gly His Gly His 530 535 540Trp Ala Tyr His Trp Asn Gly Asp Ile Leu Ser Asp Trp Ser Ser Met545 550 555 560Arg Trp Thr Ile Pro Ser Ile Leu Asn Phe Asn Met Phe Gly Ile Pro 565 570 575Met Val Gly Ala Asp Ile Xaa Gly Phe Gly Gly Asn Thr Ala Glu Glu 580 585 590Leu Xaa Ile Arg Trp Tyr Gln Leu Gly Ala Phe Tyr Ser Phe Ala Arg 595 600 605Asn His Asn Asp Ile His Ser Ile Asp Gln Asp Pro Ala Ala Leu Gly 610 615 620Glu Ser Val Ile Arg Ala Ala Arg Ser Ser Leu Gln Tyr Arg Tyr Arg625 630 635 640Phe Leu Ala His Leu Tyr Thr Leu Phe Tyr His Val His Lys Asn Gly 645 650 655Gly Thr Val Leu Arg Pro Met Phe Phe Glu Phe Pro His Asp Glu His 660 665 670Thr Tyr Glu Ile Glu Thr Gln Phe Met Trp Gly Asp Ser Val Leu Ile 675 680 685Ala Pro Ile Leu Tyr Pro Asn Gln Thr Gln His Lys Ile Tyr Leu Pro 690 695 700Lys Gly Thr Trp Tyr Asn Arg Lys Val Ser Phe Glu Ser Gln Gly Gln705 710 715 720Tyr Ile Thr Met Asn Asp Ser Tyr Asp Asp Ile Asp Tyr Val Phe Val 725 730 735Arg Gly Gly Ser Ile Ile Pro Thr Gln Glu Pro His Asp Asn Thr Glu 740 745 750Leu Met Lys Thr Lys Asp Phe Leu Leu Ile Val Ala Leu Asp Asn Gln 755 760 765Thr Ser Tyr Ala Lys Gly Ser Leu Tyr Trp Asp Ser Gly Asp Ser Leu 770 775 780Asn Pro Asp Lys Thr Gly His Tyr Asn Phe Tyr Asn Phe Asp Ala Val785 790 795 800Asn Asn Thr Leu Thr Ile Gln Ser Gln Trp Leu Gly Tyr Gln Thr Thr 805 810 815Gln Asn Ile Asn Phe Ile Asn Ile Leu Gly Val Pro Lys Leu Pro Thr 820 825 830Ser Phe Lys Leu Asn Gly His Val Ser Asp Pro Arg Ile Ile Arg Phe 835 840 845Asn Tyr Asp Glu Gln Thr Asn Ile Leu Thr Val Glu Thr Lys Leu Pro 850 855 860Ile Tyr Asn Gln Asp Ser Ser Ser His Asp Arg Ile His Tyr Gln Phe865 870 875 880Glu Trp Ile Met Glu 885303975PRTDermatophagoides farinaemisc_feature(12)..(12)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(17)..(17)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(148)..(148)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(316)..(316)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(370)..(370)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(426)..(426)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(449)..(449)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(457)..(457)Xaa is serine, alanine, or 2-aminobutyric acid 303Val Val Ile Lys Val Glu Asn Leu Pro Glu Arg Xaa Asp Tyr Ser Gln1 5 10 15Xaa Pro Lys Trp Asp Pro Asn Asp Ile Asn Val His Leu Val Ala His 20 25 30Thr His Asp Asp Val Gly Trp Leu Lys Thr Val Glu Gln Tyr Tyr Tyr 35 40 45Gly Leu Lys Asn Asp Ile Gln Arg Ala Gly Val Gln Tyr Ile Leu Asp 50 55 60Thr Val Ile Glu Glu Leu Ile Arg Asn Lys Gln Arg Arg Phe Ile Tyr65 70 75 80Val Glu Ile Ala Phe Phe Trp Lys Trp Trp Gln Glu Gln Asp Glu Asp 85 90 95Gln Arg Met Ile Val Arg Glu Leu Val Arg Thr Gly Gln Leu Glu Phe 100 105 110Ile Asn Gly Gly Trp Ser Met Pro Asp Glu Ala Ala Thr His Tyr Asn 115 120 125Ser Leu Ile Asp Gln Ser Thr Trp Gly Leu Arg Gln Leu Asn Asp Thr 130 135 140Phe Gly Lys Xaa Gly His Pro Lys Val Thr Trp Gln Ile Asp Pro Phe145 150 155 160Gly His Ser Arg Glu Met Ala Asn Leu Tyr Ala Gln Met Gly Tyr Asp 165 170 175Ala Leu Phe Phe Ala Arg Gln Asp Tyr Gln Asp Arg Glu Asn Arg Met 180 185 190Thr Asn Arg Lys Leu Glu His Val Trp Gln Gly Ser Asp Asp Leu Gly 195 200 205Thr Ala Gly Asp Ile Phe Thr Gly Met Met Phe Ser Gly Tyr Gly Pro 210 215 220Ile Glu Phe Asn Trp Asp Ile Thr Asn Gly Pro Glu Asp Ala Val Val225 230 235 240Asp Asn Pro Glu Ser Glu Glu Tyr Asn Val Pro Asp Lys Ile Arg Arg 245 250 255Phe Val Glu Lys Ala Lys Tyr Phe Ala Gln Tyr Tyr Ala Thr Asn His 260 265 270Phe Met Phe Pro Met Gly Thr Asp Phe Gln Tyr Gly Asp Ala His Thr 275 280 285Trp Phe Lys Asn Leu Asp Lys Leu Ile Lys Ala Val Asn Asn Ala Gly 290 295 300Lys Gly Val Arg Ala Phe Tyr Ser Thr Pro Ser Xaa Tyr Ala Arg Ala305 310 315 320Leu Tyr Glu Thr Asn Arg Thr Trp Thr Thr Lys Thr Asp Asp Phe Phe 325 330 335Pro Tyr Ala Ser Asp Glu His Ala Tyr Trp Thr Gly Tyr Phe Thr Ser 340 345 350Arg Pro Ala Leu Lys Arg Met Glu Arg Met Gly Asn Asn Leu Leu Gln 355 360 365Ala Xaa Lys Gln Leu Asp Ile Leu Ala Gly Asn Asp Gly Arg Phe Glu 370 375 380Met Asn Ile Thr Arg Leu Arg Glu Ala Met Gly Val Met Gln His His385 390 395 400Asp Ala Val Thr Gly Thr Glu Lys Gln His Val Ala Phe Asn Tyr Ala 405 410 415Lys Met Leu Asp Ser Ala Met Leu Gln Xaa Arg His Val Ile Ser Glu 420 425 430Ser Tyr Arg Lys Leu Phe Pro Thr Gln Thr Lys Glu Gln His Glu Phe 435 440 445Xaa Pro Tyr Leu Asn Ile Ser Ser Xaa Pro Ser Thr Glu Met Gly Glu 450 455 460Ser Arg Thr Ile His Leu Tyr Asn Pro Leu Gly His Arg Leu Val Asn465 470 475 480Arg Thr Ile Arg Val Pro Val Lys Asp Gly Tyr Tyr Tyr Gln Val Arg 485 490 495Asp Gln Asn Asp His Ser Ile Pro Ala Val Leu Ile Ser Ile Pro Glu 500 505 510Phe Val Arg Lys Ile Pro Gly Arg Lys Ser Val Ala Thr Lys Glu Leu 515 520 525Val Phe Arg Val Pro Ile Ile Glu Ser Leu Gly Ile Arg Arg Phe His 530 535 540Met Ile Ala Thr Lys Glu Lys Gln Gln Asp Ser Ala Val Glu Ile Gln545 550 555 560Gly Glu Lys Phe Val Gly His Lys Gly Gln Arg Phe Gln Leu Lys Asp 565 570 575Gly Leu Ile Ile Glu Phe Asp Ser Asn Gly Lys Ile Ala Thr Met Ile 580 585 590Arg Asn Asn Gln Ser Ile Ser Ile Ser Asn Glu Phe Arg Leu Phe His 595 600 605Gly Ala Asp Ile Gly Arg His Ser Gly Ala Tyr Ile Phe Arg Pro Ser 610 615 620Glu Gln Lys Thr Phe Pro Val Thr Glu Lys Met Glu Ala Thr Leu Tyr625 630 635 640Val Asp Gln Lys Phe Gly Ile Val Gln Glu Val His Gln Gln Phe Asp 645 650 655Ser Phe Val Gly Gln Ile Ile Arg Leu Asp Lys Gln Gly Asp Tyr Val 660 665 670Glu Phe Asp Phe Val Val Gly Pro Ile Pro Val Asp Asp Leu Ile Gly 675 680 685Lys Glu Ile Ile Thr Arg Tyr Asn Thr Asn Leu Ala Asn Asp Glu Thr 690 695 700Phe Phe Thr Asp Ser Asn Gly Arg Gln Met Leu Arg Arg Arg Trp Asn705 710 715 720Tyr Arg Pro Ser Trp Lys Tyr Glu Ile Glu Glu Pro Val Ser Gly Asn 725 730 735Tyr Tyr Pro Val Asn Ser Arg Ile Ala Ile Arg Asp Asp Arg Lys Ser 740 745 750Leu Gln Met Thr Ile Met Thr Asp Arg Ser Gln Gly Gly Ser Leu Ser 755 760 765Pro Glu Gln Ile Asn Gly Ser Val Asp Leu Met Val His Arg Arg Leu 770 775 780Leu His Asp Asp Tyr Phe Gly Val Asp Glu Pro Leu Asn Glu Pro Gly785 790 795 800Val Asp Gly His Gly Ile Val Ile Arg Gly Arg His Leu Leu Leu Leu 805 810 815Asp Thr Leu Glu Lys Ala Ala Glu Lys His Arg Pro Leu Ala Gln Glu 820 825 830Met Phe Met Glu Pro Ile Ile Ser Phe Thr Ser Ser Met Glu Lys Asn 835 840 845Gln Pro Ile Tyr Lys Gly Leu Thr Lys Asp Leu Pro Gly Asn Val His 850 855 860Leu Leu Thr Leu Glu Gln Trp His Ser Lys Arg Tyr Leu Leu Arg Leu865 870 875 880Glu His Phe Tyr Gln Arg Phe Glu Asp Pro Ser Leu Ser Asn Pro Ala 885 890 895Thr Val Ser Leu Arg His Leu Phe Gln Ser Phe Glu Ile Thr Ala Val 900 905 910Glu Glu Leu Thr Leu Gly Ala Asn Gln Pro Ile Ser Ala Leu Lys Asn 915 920 925Arg Leu Gln Tyr Arg Tyr Ile Arg Pro Leu Asn Glu Gln Gln Ser Ser 930 935 940Ile Ile Thr Asp Pro Ile Ile Glu Gly Glu Asn Phe Asp Ile His Leu945 950 955 960Glu Pro Met Gln Ile Arg Thr Phe Leu Ile Asp Ile Lys Arg Asn 965 970 975304990PRTDermatophagoides pteronyssinusmisc_feature(12)..(12)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(17)..(17)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(148)..(148)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(316)..(316)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(370)..(370)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(426)..(426)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(449)..(449)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(457)..(457)Xaa is serine, alanine, or 2-aminobutyric acid 304Val Val Ile Lys Val Glu Asn Leu Pro Glu Gln Xaa Asp Tyr Thr Gln1 5 10 15Xaa Pro Lys Trp Ser Lys Asp Asp Ile Asn Val His Leu Val Ala His 20 25 30Thr His Asp Asp Val Gly Trp Leu Lys Thr Val Glu Gln Tyr Tyr Tyr 35 40 45Gly Leu Lys Asn Asp Ile Gln Arg Ala Gly Val Gln Tyr Ile Leu Asp 50 55 60Thr Met Ile Glu Glu Leu Ile Arg Asn Lys Asp Arg Arg Phe Ile Tyr65 70 75 80Val Glu Ile Ala Phe Phe Trp Lys Trp Trp Gln Glu Gln Asn Glu Glu 85 90 95Gln Arg Met Ile Val Lys Glu Leu Val Arg Thr Gly Gln Leu Glu Phe 100 105 110Ile Asn Gly Gly Trp Ser Met Pro Asp Glu Ala Ala Thr His Tyr Asn 115 120 125Ser Leu Ile Asp Gln Ser Thr Trp Gly Leu Arg Gln Leu Asn Asp Thr 130 135 140Phe Gly Arg Xaa Gly His Pro Lys Val Thr Trp Gln Ile Asp Pro Phe145 150 155 160Gly His Ser Lys Glu Met Ala Asn Leu Tyr Ala Gln Met Gly Tyr Asp 165 170 175Ala Leu Phe Phe Ala Arg Gln Asp Tyr Gln Asp Arg Glu Asn Arg Met 180 185 190Ser Asn Arg Thr Leu Glu His Val Trp Gln Gly Ser Asp Asp Leu Gly 195 200 205Glu Ile Gly Asp Ile Phe Thr Gly Met Met Phe Ser Gly Tyr Gly Pro 210 215 220Ile Glu Phe Asn Trp Asp Ile Thr Asn Gly Pro Glu Asp Ala Val Val225 230 235 240Asp Asn Pro Glu Ser Glu Glu Tyr Asn Val Pro Asp Lys Ile Arg Arg 245 250 255Phe Val Glu Lys Ala Lys Tyr Phe Gly Gln Phe Tyr Ala Thr Asn His 260 265 270Phe Met Phe Pro Met Gly Thr Asp Phe Gln Tyr Thr Asp Ala His Thr 275 280 285Trp Phe Lys Asn Leu Asp Lys Leu Ile Asn Ala Val Asn Lys Ala Gly 290 295

300Lys Gly Val Arg Ala Phe Tyr Ser Thr Pro Ser Xaa Tyr Ala His Ala305 310 315 320Leu Tyr Glu Gln Asn Arg Thr Trp Thr Thr Lys Thr Asp Asp Phe Phe 325 330 335Pro Tyr Ala Ser Asp Glu His Ala Tyr Trp Thr Gly Tyr Phe Thr Ser 340 345 350Arg Pro Ala Ile Lys Arg Met Glu Arg Ile Gly Asn Asn Leu Leu Gln 355 360 365Ala Xaa Lys Gln Leu Asp Val Leu Ala Asp Asn Asn Gly Arg Phe Glu 370 375 380Met Asn Leu Thr Lys Met Arg Glu Ala Met Gly Val Met Gln His His385 390 395 400Asp Ala Val Thr Gly Thr Glu Lys Gln His Val Ala Phe Asn Tyr Ala 405 410 415Lys Met Leu Asp Ser Ala Met Leu Gln Xaa Arg His Ile Ile Asn Glu 420 425 430Ser Tyr Lys Lys Leu Leu Pro Lys Ser Ser Thr Ser Glu His Glu Phe 435 440 445Xaa Pro Tyr Leu Asn Ile Ser Ser Xaa Pro Thr Thr Glu Met Gly Glu 450 455 460Ser Arg Ile Ile Tyr Leu Tyr Asn Pro Leu Gly His Arg Leu Ile Asn465 470 475 480His Thr Val Arg Leu Pro Ile Lys Asn Gly Tyr Tyr Tyr Arg Ile Gln 485 490 495Asp Gln Asn Asn Gln Ser Val Pro Ser Val Leu Val Pro Ile Pro Glu 500 505 510Phe Val Gln Lys Ile Pro Gly Arg Lys Ser Val Ala Thr Lys Glu Leu 515 520 525Val Phe Arg Val Pro Val Ile Glu Pro Leu Gly Ile Thr Thr Met Tyr 530 535 540Met Tyr Val Asp Lys Asn Glu Gln Pro Asn Ser Ala Ile Glu Ile Lys545 550 555 560Gly Glu Asn Pro Asp Asp Asn Asp Asp Lys Ser Lys Trp Leu Val Leu 565 570 575Thr Lys Asn Leu Ile Val Glu Phe Tyr Ser Asn Gly Thr Ile Ser Arg 580 585 590Ile Ser Ile Asp Lys Leu His Gln Ser Ile Ser Ile Ser Asn Glu Phe 595 600 605Arg Leu Tyr His Gly Ala Gly Gly Thr Gly Arg His Ser Gly Ala Tyr 610 615 620Ile Phe Arg Pro Asn Glu Gln Lys Thr Phe Pro Val Thr Asn Lys Ile625 630 635 640Lys Ser Thr Phe Phe Ile Asp Arg Lys Tyr His Ile Val Gln Glu Val 645 650 655His Gln Gln Phe Asp Ser Ser Phe Val Gly Gln Ile Ile Arg Met Asp 660 665 670Lys Tyr Asn Asp Asn Val Glu Phe Asp Phe Val Val Gly Pro Ile Pro 675 680 685Val Asn Asp Gln Ile Gly Lys Glu Ile Ile Ala Ser Tyr Lys Thr Asp 690 695 700Leu Glu Asn Asp Glu Thr Phe Tyr Thr Asp Ala Asn Gly Arg Gln Met705 710 715 720Leu Arg Arg Arg Trp Asn Tyr Arg Pro Ser Trp Lys Tyr Asn Val Gln 725 730 735Glu Pro Ile Ser Gly Asn Tyr Tyr Pro Val Asn Ser Arg Ile Ala Ile 740 745 750Arg Asp Glu Lys Gln Ser Leu Gln Met Thr Ile Met Thr Asp Arg Ser 755 760 765Gln Gly Gly Ser Leu Ser Pro Glu Gln Ile Asn Gly Ser Ile Asp Ile 770 775 780Met Ile His Arg Arg Leu Leu His Asp Asp Tyr Phe Gly Val Gly Glu785 790 795 800Ala Leu Asn Glu Pro Gly Val Asp Gly His Gly Leu Val Ile Arg Gly 805 810 815Lys His Leu Leu Leu Leu Asn Ser Ile Lys Gln Ser Ala Ser Glu His 820 825 830Arg Pro Leu Ala Gln Gln Met Phe Met Glu Pro Ile Ile Ser Phe Thr 835 840 845Ser Ile Glu Ser Asn Lys Gln Ala Glu Lys Gln Ser Asn Gln Tyr Ile 850 855 860Gly Leu Asn Asn Asp Leu Pro Ser Asn Val His Leu Leu Thr Leu Glu865 870 875 880Gln Trp His Ser Lys Arg Tyr Leu Leu Arg Leu Glu His Phe Tyr Gln 885 890 895Ser Asn Glu Asp Thr Glu Leu Ser Lys Pro Val Lys Leu Ser Leu Arg 900 905 910His Leu Phe Lys Ser Phe Glu Ile Ile Ala Val Glu Glu Leu Thr Leu 915 920 925Gly Ala Asn Gln Pro Ile Ser Ser Leu Lys Asn Arg Leu His Tyr Arg 930 935 940Tyr Asn Arg Pro Leu Glu Gln Arg Gln Gln Gln Gln Ser Ser Leu Leu945 950 955 960Leu Asp Asp Pro Lys Ile Glu Gly Glu Asn Phe Asp Ile His Leu Ser 965 970 975Pro Met Gln Ile Arg Thr Phe Leu Ile Asp Ile Lys Arg Asn 980 985 990305125PRTBlomia tropicalis 305Gly Lys Tyr Gln Leu Glu Ser Ser Glu Asn Phe Asp Glu Phe Leu Lys1 5 10 15Glu Leu Gly Val Asn Phe Ile Leu Arg Asn Leu Ala Lys Thr Ser Lys 20 25 30Pro Thr Ile Glu Ile Thr Leu Asp Gly Asp Thr Tyr Thr Ile Lys Thr 35 40 45Ile Thr Thr Leu Lys Thr Ser Val Ile Thr Phe Lys Ile Gly Glu Glu 50 55 60Phe Glu Glu Ser Arg Met Asp Gly Lys Thr Val Lys Thr Val Ile Thr65 70 75 80Gln Glu Gly Asp Lys Leu Ile Gln Val Gln Gln Gly Asp Lys Glu Val 85 90 95Lys Ile Val Arg Glu Phe Thr Glu Thr His Leu Thr Thr Ile Cys Thr 100 105 110Val Gly Glu Ile Thr Ser Thr Arg Val Tyr Lys Arg Val 115 120 125306363PRTBlomia tropicalis 306Met Ser Ile Ile Gln Asn Leu Pro Ala Asp Val Gln Glu Glu Leu Arg1 5 10 15Lys Thr Ala Asn Ala Ile Val Thr Pro Gly Lys Gly Ile Leu Ala Ala 20 25 30Asp Glu Ser Thr Gly Thr Ile Gly Lys Arg Phe Ala Asp Ile Asn Val 35 40 45Glu Asn Val Glu Asn Asn Arg Arg Thr Tyr Arg Asp Leu Leu Phe Ser 50 55 60Ala Pro Asp Glu Val Asn Asn Tyr Ile Ser Gly Val Ile Leu Phe Asp65 70 75 80Glu Thr Val Tyr Gln Lys Asn Ala Ala Gly Val Pro Phe Pro Gln Val 85 90 95Leu Ala Lys Arg Gly Ile Ile Pro Gly Ile Lys Val Asp Thr Gly Val 100 105 110Val Val Leu Gln Gly Thr Asn Gly Glu Ser Thr Thr Gln Gly Leu Asp 115 120 125Asn Leu Thr Lys Arg Cys Gln Ala Tyr Tyr Glu Gln Gly Cys Arg Phe 130 135 140Ala Lys Trp Arg Cys Val Leu Lys Ile Gly Asp Asn Glu Pro Ser Pro145 150 155 160Leu Ala Ile Leu Glu Asn Ala Asn Val Leu Ala Arg Tyr Ala Ser Cys 165 170 175Cys Gln Gln Ala Arg Ile Val Pro Ile Val Glu Pro Glu Ile Leu Pro 180 185 190Asp Gly Ala His Asp Ile Glu Arg Cys Gln Lys Val Thr Glu Lys Val 195 200 205Leu Ala Ala Val Tyr Lys Ala Leu Asn Asp His Asn Val Phe Leu Glu 210 215 220Gly Thr Leu Leu Lys Pro Asn Met Val Thr Ala Gly Gln Ser Phe Ala225 230 235 240Gly Pro Lys Pro Ser Pro Gln Glu Val Ala Arg Ala Thr Val Thr Ala 245 250 255Leu Gln Arg Thr Val Pro Ala Ala Val Pro Gly Ile Val Phe Leu Ser 260 265 270Gly Gly Gln Ser Glu Glu Glu Ala Ser Ile Asn Leu Asn Ala Ile Asn 275 280 285Gln Phe Glu Gly Lys Lys Pro Trp Ala Leu Ser Phe Ser Tyr Gly Arg 290 295 300Ala Leu Gln Ala Ser Val Leu Arg Ala Trp Gln Gly Lys Asp Glu Leu305 310 315 320Ile Ala Ala Gly Gln Lys Glu Leu Val Asn Arg Ser Lys Ala Asn Ser 325 330 335Asp Ala Ser Leu Gly Lys Tyr Ser Gly Gly Ile Val Gly Ala Ala Gly 340 345 350Glu Gln Asp Leu Phe Ile Lys Asp His Gln Tyr 355 360307973PRTBlomia tropicalis 307Val Val Ile Lys Val Glu Asn Leu Pro Ala Arg Cys Asp Tyr Thr Lys1 5 10 15Cys Pro Lys Ser Asp Pro Asn Lys Ile Asn Val His Leu Val Pro His 20 25 30Thr His Asp Asp Val Gly Trp Leu Lys Thr Val Glu Gln Tyr Tyr Tyr 35 40 45Gly Ser Lys Thr Tyr Tyr Gln Lys Ala Gly Val Gln Tyr Ile Leu Asp 50 55 60Ser Val Met Asn Glu Leu Ile His Asn Lys Glu Arg Lys Phe Ile Tyr65 70 75 80Val Glu Thr Ala Phe Phe Trp Lys Trp Trp Met Glu Gln Asp Tyr Gly 85 90 95Met Arg Asn Ile Val Lys Glu Leu Val Glu Thr Gly Gln Leu Glu Phe 100 105 110Ile Asn Ala Gly Trp Ser Met Asn Asp Glu Ala Ser Thr His Tyr Asn 115 120 125Ser Ile Ile Asp Gln Met Ser Trp Gly Phe Tyr Arg Leu Gln Thr Thr 130 135 140Phe Gly Arg Cys Gly Val Pro Lys Val Ala Trp Gln Ile Asp Pro Phe145 150 155 160Gly His Ser Lys Glu Gln Ala Ala Leu Phe Ala Leu Met Asn Phe Asp 165 170 175Ala Leu Phe Phe Ala Arg Glu Asp Trp Gln Glu Gln Ser His Arg Arg 180 185 190Lys Asn Arg Thr Leu Glu His Val Trp Gln Ala Ser Ser Asp Leu Gly 195 200 205Lys Ser Ala Asp Leu Phe Thr Gly Met Met Asn Phe Gly Tyr Gly Pro 210 215 220Pro Gln Gly Phe Asn Trp Asp Leu Val Gly Gly Ala Asp Glu Pro Val225 230 235 240Ile Asp Asp Pro Glu Ser Asp Glu Tyr Asn Val Pro Arg Arg Val Lys 245 250 255Glu Leu Ile Asp Leu Ala Lys Thr Tyr Gln Lys Tyr Tyr Ala Thr Asn 260 265 270Asn Val Met Phe Pro Met Gly Thr Asp Phe Gln Tyr Gln Asp Ala His 275 280 285Ile Tyr Phe Lys Asn Met Asp Lys Leu Ile Lys Tyr Val Asn Glu Asn 290 295 300Ser Thr Glu Val Asn Ile Phe Tyr Ser Thr Pro Ser Cys Tyr Ala Lys305 310 315 320Ser Leu Lys Asp Ser Gly Lys Thr Phe Thr Ala Lys Asn Asp Asp Tyr 325 330 335Phe Pro Tyr Ala Ser Asp Pro His Ser Tyr Trp Thr Gly Tyr Phe Thr 340 345 350Ser Arg Pro Ala Ile Lys Arg Phe Glu Arg Val Gly Asn Asn Tyr Leu 355 360 365Gln Val Cys Lys Gln Met Asp Thr Tyr Thr Gly His Gln Ala Thr Arg 370 375 380Asp Arg His Thr Thr Lys Leu Arg Glu Ile Met Gly Val Met Gln His385 390 395 400His Asp Ala Val Ser Gly Thr Glu Lys Gln His Val Ala Phe Asn Tyr 405 410 415Ala Lys His Leu Gln Ser Gly Ile Glu Ser Cys Arg Lys Val Ile Ser 420 425 430Glu Ala Tyr Gln Leu Leu Gln His Pro His Thr Lys Thr Val Gln Thr 435 440 445Phe Cys Asp Tyr Leu Asn Ile Ser Ser Cys Ala Ile Thr Glu Ser Gly 450 455 460Gln Asn Phe Val Val Asn Ile Tyr Asn Pro Leu Ser Lys Thr Leu Lys465 470 475 480Asn His Pro Ile Arg Leu Pro Ile Asn Ser Asp Lys Tyr Tyr Asn Val 485 490 495Val Asp Asp Glu Gly Lys Ser Val Tyr Ser Glu Leu Thr Phe Ile Pro 500 505 510Glu Tyr Val Gln Ala Ile Pro Glu Arg Thr Thr Asn Ala Thr Thr Asp 515 520 525Leu Val Phe Leu Ala Ser Ile Pro Pro Leu Gly Tyr Ala Ser Tyr Phe 530 535 540Val Gln Ala Thr Thr Thr Lys Ser Pro Asp Ser Ala Asn Ala Val Thr545 550 555 560Val Thr Lys Ile Thr Asn Glu Thr Arg Leu Ser Ser Gly Asn Phe Ser 565 570 575Val Val Phe Asp Ser Thr Gly Ala Leu Ser Lys Val Glu Leu Pro Ser 580 585 590Gly Glu Ser Ile Pro Phe Lys Asn Glu Phe Arg Tyr Tyr Asn Gly Ala 595 600 605Ala Asp Asn Ile Arg Ala Ser Gly Ala Tyr Ile Phe Arg Pro Lys Glu 610 615 620Gln Gln Thr Phe Pro Phe Ala Lys Leu Val Ser Ala Asn Leu Leu Thr625 630 635 640Arg Thr Ser Ser Gly Gly Ile Val His Glu Val His Gln Lys Phe Asp 645 650 655Ser Asn Val Glu Gln Val Ile Arg Val Leu Pro Asp Ser Asp Ser Ile 660 665 670Glu Phe Glu Tyr Val Val Gly Pro Ile Pro Val Lys Asp Gly Ile Gly 675 680 685Lys Glu Val Val Leu Thr Tyr Glu Thr Asp Phe Lys Asn Asn Lys Thr 690 695 700Phe Tyr Thr Asp Ala Asn Gly Arg Gln Met Met Lys Arg Lys Trp Asp705 710 715 720Tyr Arg Pro Glu Phe Lys Met Glu Val Thr Glu Pro Ile Ser Gly Asn 725 730 735Tyr Tyr Pro Ile Asn Ser Arg Ile Tyr Leu Gln Asp Glu Lys Lys Gly 740 745 750Met Gln Met Thr Ile Leu Asn Asp Arg Ser Gln Gly Gly Thr Ser Pro 755 760 765Arg Asp Gly Val Ile Glu Ile Met Val His Arg Arg Leu Leu His Asp 770 775 780Asp Gly Phe Gly Val Gly Glu Ala Leu Asn Glu Pro Gly Val Asp Asn785 790 795 800Lys Gly Leu Ile Ile Arg Gly Arg His Leu Val Gln Phe Ser Asp Ile 805 810 815Lys Thr Ala Ala Ser Lys His Arg Pro Lys Ala Gln Gln Leu Phe Met 820 825 830Ala Pro Val Leu Ser Phe Val Pro Asp Val Ser Asp Tyr Glu Thr Tyr 835 840 845Lys Arg Ser His Leu Thr Lys Tyr Ser Ala Leu Ile Asn Pro Leu Pro 850 855 860Glu Gln Ile His Leu Leu Thr Leu Glu Arg Trp Met Glu Gly His Phe865 870 875 880Leu Leu Arg Leu Glu His Tyr Phe Gln Thr Asn Glu Asp Ala Glu Leu 885 890 895Ser Lys Pro Val Thr Leu Asn Leu Lys His Met Phe Lys Ser Phe Lys 900 905 910Ile Phe Glu Ala Glu Glu Leu Thr Leu Gly Gly Asn Gln Pro Ile Phe 915 920 925Glu Thr Lys His Arg Met Lys Phe Asn Tyr Ile Pro Val Glu Asn Val 930 935 940Thr Glu Pro Pro Glu His Ser Phe Asp Pro Thr Lys Leu Glu Val Lys945 950 955 960Leu Tyr Pro Met Gln Ile Arg Thr Phe Ser Val Arg Val 965 970308889PRTBlomia tropicalis 308Gln Cys Met Ala Ile Pro Pro Asn Ser Arg Ile Asp Cys Asn Pro Asp1 5 10 15Pro Pro Ile Ser Ala Glu Val Cys Gln Ser Arg Gly Cys Cys Trp Met 20 25 30Pro Ser Ser Asn Glu Ser Ser Glu Asn Met Asn Leu Leu Lys Lys Asn 35 40 45Val Leu Pro Pro Leu Asn Val Pro Tyr Cys Phe Phe Gly Ser Asp Tyr 50 55 60His Gly Tyr Asn Val Ser Asn Val Gln Thr Ile Asn Asp Asn Gln Lys65 70 75 80Val Ile Asn Leu Gln Arg Ile Arg Asp Ser Gly Phe Val Asn Asp Val 85 90 95Lys Asn Val Arg Ile Gln Ile Asp Glu Leu Ser Ser Asn Val Leu Arg 100 105 110Ile Lys Met Ile Asp Ser Asp Ser Ser Arg Tyr Glu Val Pro Ile Pro 115 120 125Val Leu Asn Leu Pro Lys Arg Asn Glu Val Leu Glu Ser Leu Asn Glu 130 135 140Lys Met Tyr Gln Val Glu Met Asn Ser Thr Asp Phe Met Leu Thr Val145 150 155 160Tyr Arg Ala Lys Thr Lys Ala Ile Val Phe Asn Val Asn Leu Gly Gln 165 170 175Leu Ile Tyr Ser Asn Gln Phe Ile Gln Ile Thr Asn Lys Leu Ala Ser 180 185 190Asn Phe Ile Phe Gly Ile Gly Glu Asn Arg Glu Ser Phe Arg Lys Leu 195 200 205Thr Asn Trp Lys Arg Tyr Thr Leu Phe Ala Arg Asp Gln Trp Pro Val 210 215 220Pro Asp Arg Ala Leu Tyr Gly Ser His Pro Phe Tyr Leu Ala Thr Glu225 230 235 240Ser Asp Asn Ser Ser His Gly Val Phe Leu Phe Asn Ser Asn Ala Met 245 250 255Asp Ile Ile Thr Gln Pro Met Pro Ala Ile Thr Tyr Arg Thr Ile Gly 260 265 270Gly Ile Leu Asp Phe Phe Leu Phe Leu Gly Pro Thr Ser Glu Asn Val 275 280 285Ile Glu Gln Tyr His Gln Leu Ile Gly Leu Pro Thr Met Pro Ala Tyr 290 295 300Trp Thr Leu Gly Phe His Leu Ser Arg Tyr Gly

Tyr Arg Asn Leu Ser305 310 315 320Asn Leu Glu Lys Thr Phe Arg Arg Thr Arg Lys Ala Glu Ile Pro Phe 325 330 335Asp Val Gln Trp Thr Asp Ile Asp Met Phe Asp Ser Asn Asn Asp Phe 340 345 350Thr Tyr Asp Arg Lys Arg Phe Asp Gly Leu Pro Lys Phe Ile Glu His 355 360 365Leu His Ser Ile Asn Met Arg Phe Val Pro Met Phe Asp Cys Gly Ile 370 375 380Ser Ser Gly Glu His Pro Pro Gln Ser Tyr Leu Pro Tyr Lys Met Gly385 390 395 400Leu Glu Met Asn Val Phe Val Arg Asn Gly Thr Asn Gln Pro Phe Glu 405 410 415Gly Lys Val Trp Asn Ser Lys Ser Thr Val Trp Pro Asp Phe Thr His 420 425 430Pro Asn Ala Thr Lys Tyr Trp Thr Arg Gln Phe Ala Glu Tyr His Lys 435 440 445Thr Ile Gln Phe Asp Gly Ala Trp Ile Asp Met Asn Glu Pro Ser Asn 450 455 460Phe Leu Asp Gly Ala Phe Asn Gly Cys Pro Thr Asn Ser Thr Leu Glu465 470 475 480Thr Pro Gln Tyr Thr Pro Gly Met Val Glu Asp Ser Leu Thr Leu Asn 485 490 495His Lys Thr Leu Cys Met Ser Ala Arg His Ser Ile Gly Leu His Tyr 500 505 510Asn Leu His Asn Leu Tyr Gly Ile Ser Glu Ala Ile Val Thr Lys Ser 515 520 525Ala Leu Glu Ser Val Leu Lys Arg Arg Ser Phe Ile Leu Ser Arg Ser 530 535 540Thr Ala Pro Gly His Gly His Phe Ala Ala His Trp Asp Gly Asp Ile545 550 555 560Leu Ser Asp Trp Pro Ser Met Lys Trp Ser Ile Ser Ser Ile Leu Asn 565 570 575Phe Asn Ile Phe Gly Val Pro Leu Ile Gly Ala Asp Ile Cys Gly Phe 580 585 590Asn Gly Asn Thr Thr Ile Glu Leu Cys Ala Arg Trp His Gln Leu Gly 595 600 605Ala Phe Tyr Thr Phe Val Arg Asn His Asn Thr Asp Asn Ala Ile Asp 610 615 620Gln Asp Pro Val Ala Leu Gly Pro Leu Val Val Lys Ala Ala Lys Asn625 630 635 640Ala Leu Lys Leu Arg Tyr Ala Leu Leu Pro Tyr Leu Tyr Thr Gln Phe 645 650 655Tyr Arg Val His Arg Lys Gly Gly Thr Ile Leu Arg Pro Leu Phe Phe 660 665 670Glu Phe Val His Asp Gln Val Val Leu Glu Ile Glu Thr Gln Phe Met 675 680 685Trp Gly Ser Ser Ile Met Val Ala Pro Ala Leu Ser Ile Asn Glu Thr 690 695 700Glu Thr Ser Val Tyr Phe Pro Ser Gly Thr Trp Phe His Ser Tyr Asn705 710 715 720Phe Thr Arg Ile Asn Thr Ile Gly Lys Phe Leu Pro Gln Leu Ala Ser 725 730 735Phe Asp Tyr Pro Asn Val Tyr Phe Arg Ala Gly Ser Ile Ile Pro Thr 740 745 750Leu Arg Pro Met Leu Thr Thr Asp Glu Thr His Ser Gly Asn Phe Thr 755 760 765Leu Leu Val Ala Leu Ser Asn Glu Asn Gly His Ala Glu Gly Asp Leu 770 775 780Tyr Leu Asp Ser Gly Asp Gly Leu Asp Thr Glu Val Leu Gly His Tyr785 790 795 800Asn Leu Tyr Ser Phe Lys Val Glu Lys Lys Ile Leu Glu Ile Lys Ser 805 810 815Ser His Leu Gly Tyr Ser Thr Glu Gln Met Ile Asp Asn Val Leu Ile 820 825 830Leu Gly Ile Asp Lys Ser Pro Ile Glu Ile Lys Ile Asn Gly Arg Ser 835 840 845Met Lys Ser Trp Ser Tyr Ser Lys Asn Lys Ile His Ile Asn Ser Leu 850 855 860Asn Leu Pro Leu Tyr Asp Leu Lys Thr Ile Asp Lys Ser Lys Leu Ile865 870 875 880Gln Ile His Tyr Gln Ile Glu Trp Val 885309482PRTBlomia tropicalis 309Gly Cys Phe Arg Ala Ala Val Leu Asp His Val His Gln Ser Ser Arg1 5 10 15Asn Gly Gly Gly Thr Lys Glu Asn Ile Lys Leu Asn Leu Lys Leu Tyr 20 25 30Glu Thr Ala Ala Lys Thr Ala Lys Glu Gln Gly Ala Asp Ile Ile Val 35 40 45Phe Pro Glu Asn Gly Ile Val Tyr Gly Ile Gly Ser Arg Ala Asn Ala 50 55 60Leu Lys Tyr Gly Glu Ile Leu Pro Glu Ser Lys Thr Ser Met Cys Thr65 70 75 80Asp Ser Tyr Ala Ser Ser His Pro Ile Ala Tyr Gln Leu Ala Cys Leu 85 90 95Ala Lys Glu His Gln Met Phe Val Ala Ala Asp Met Ile Asp Val Gln 100 105 110Thr Cys Gln Thr Lys Ser Cys Pro Ile Asp Lys Lys Tyr Ala Phe Asn 115 120 125Thr Ala Val Leu Phe Asp Arg Asn Gly Tyr Leu Leu Gly Lys Tyr His 130 135 140Lys Met His Pro Phe Gly Glu Leu Gln Phe Asn Val Pro Pro Lys Asp145 150 155 160Glu Leu Val Val Ile Glu Thr Glu Ile Gly Arg Leu Ser Met Gln Val 165 170 175Cys Phe Asp Leu Ile Tyr Asn Lys Pro Gly Val Val Leu Ala Ser Gln 180 185 190Asp Lys Ile Asp Thr Met Leu Phe Pro Thr Trp Trp Phe Asp Glu Leu 195 200 205Pro Phe Leu Ala Ala Ser Gln Tyr Gln Met Ser Trp Ala Phe Gly Asn 210 215 220Lys Ile Asn Leu Leu Ala Ser Asn Ile His Leu Val Ala Val Gly Ser225 230 235 240Lys Gly Ser Gly Ile Phe Ala Gly Gly His Gly Gln Phe Glu Val Ile 245 250 255Ser Glu Pro Asp Ala Lys Ala Arg Ile Leu Val Ala Thr Leu Pro Ile 260 265 270Asn Ala Arg Ser Asp Ala Gln Cys Ser Met Asp Ser Lys Lys Ile Glu 275 280 285Val Pro Gln Met Val Pro Ile Pro Ser Asn Val Ile Tyr Asn Tyr Gln 290 295 300Met Met Asn Leu Thr Glu Asn Thr Val Lys Lys Leu Asp Pro Ser Met305 310 315 320Glu Ala Ile Ser Ala Cys Asp Gly Gly Val Cys Cys Gln Leu Asn Tyr 325 330 335Gln Met Asp Gln Ser Ser Ile Lys Ser Asp Glu Glu Tyr Tyr Leu Ile 340 345 350Val Thr Asn Arg Thr Arg Pro Gly Ala Tyr Pro Trp Thr Glu Glu Tyr 355 360 365Cys Gly Leu Val Leu Cys Pro His Met Thr Lys Leu Asp Thr Cys Lys 370 375 380Gln Ile Ser Ser Asn Asn Pro Leu Gln Thr Lys Phe Leu Tyr Ala Lys385 390 395 400Leu Ser Gly Glu Phe Ser Ser Glu Thr His Val Tyr Pro Ser Val Ile 405 410 415Gly Ser Glu His Lys Val Leu Pro Lys Asp Gly Gly Leu Trp Thr Tyr 420 425 430Glu Asp Glu Lys Thr Asp Val Gly Ala Lys Lys Gln Lys Phe Phe Ile 435 440 445Thr Phe Gly Asn Lys Glu Glu Arg Lys Ser Tyr Thr Ile Ser Thr Ile 450 455 460Gly Leu Tyr Gly Arg Val Tyr Ala Arg Asp Pro Pro Tyr Glu Gln Lys465 470 475 480Pro Leu310491PRTBlomia tropicalis 310Asp Arg Asn Lys Leu Pro His Lys Val Val Cys Tyr Trp Gly Thr Trp1 5 10 15Ala Phe Tyr Arg Pro Gly Ser Asp Gly Lys Phe Glu Ala Glu Asn Ile 20 25 30Asn Pro Asn Leu Cys Thr His Ile Asn Tyr Gly Phe Ala Lys Leu Val 35 40 45Gly Asn Lys Ile Ala Leu Phe Asp Pro Asp Leu Asp Thr Gly Asp Glu 50 55 60Asp Trp Ala Ser Gly Leu Thr Trp Gly His Gly Met Ile Arg Arg Leu65 70 75 80Asn Glu Leu Arg Lys Tyr Asn Lys Asn Leu Ser Thr Leu Ile Ser Ile 85 90 95Gly Gly Trp Asn Glu Gly Ser Asn Lys Tyr Ser Thr Met Val Ser Thr 100 105 110Ala Gly Gly Arg Ser Glu Phe Val Lys Ser Val Ile Glu Phe Leu Gln 115 120 125Lys Tyr Glu Phe Asp Gly Leu Asp Leu Asp Trp Glu Tyr Pro Gly Met 130 135 140Ser Ala Ser Gly Asp Ala Asp Arg Lys Pro Gly Arg Glu Gln Asp Lys145 150 155 160Ala Asp Tyr Ile Glu Leu Leu Lys Glu Leu Arg Gln Ala Phe Glu Pro 165 170 175His Gly Tyr Ile Leu Ser Ala Ala Val Ser Ala Gly Ala Pro Thr Ile 180 185 190Asp Arg Ala Tyr Asn Val Pro Glu Val Ser Lys His Leu His Phe Ile 195 200 205Asn Leu Met Ala Tyr Asp Phe His Gly Gly Trp Asp Thr Lys Thr Ala 210 215 220His Asn Ala Pro Leu Tyr Ala Leu Pro Gly Ala Glu Gly Ile Asp Lys225 230 235 240Glu Phe Thr Val Ser Tyr Ala Val Glu Tyr Trp Ile Ser Lys Gly Ala 245 250 255Asp Pro Lys Lys Leu Val Leu Gly Ile Pro Leu Tyr Gly Arg Thr Phe 260 265 270Thr Leu Ala Gly Pro Asn His Asp Ile Gly Ala Pro Val Thr Gly His 275 280 285Gly Gly Gln Ala Gly Pro Ile Thr Arg Leu Ile Gly Met Leu Gly Tyr 290 295 300Asn Glu Ile Cys Ser Met Val Lys Asn Gly Trp Glu Ile His Trp Asn305 310 315 320Asp Ile Gln Gln Ile Pro Tyr Ala Thr His Ala Ser Gln Trp Ile Gly 325 330 335Tyr Asp Asn Glu Lys Ser Ile Glu Lys Lys Leu Asp Tyr Val His Gln 340 345 350Lys Asn Leu Gly Gly Gly Met Val Trp Ser Ile Asp Thr Asp Asp Phe 355 360 365Ser Gly His Cys Gly Val Lys Tyr Pro Leu Leu Lys Thr Ile Ser Arg 370 375 380Arg Leu Asn Asn Ile Asp Gly Pro Asp Val Val Ile Pro Arg Thr His385 390 395 400Ala Thr Thr Pro His Pro Asp Asp His Asp His Thr Thr Lys Arg Pro 405 410 415Asp Asp Pro His Thr Asp Pro His Thr Glu Pro His His Asp Lys Thr 420 425 430Thr Ser Ala Pro Asn Pro Asp Gly Lys Phe Gln Cys His Ser Thr Gly 435 440 445Phe Phe Lys Asp Pro Ser Asp Pro Arg Lys Phe His Gln Cys Val Asp 450 455 460Ile Gly Asn Gly Lys Leu Lys Asp Tyr Glu Phe Asn Cys Pro Leu Gly465 470 475 480Ser His Tyr Asp Glu Gln Leu His Val Cys Val 485 490311459PRTBlomia tropicalis 311Asp Thr Pro Ala Asn Cys Thr Tyr Glu Asp Ile Arg Gly Glu Trp Glu1 5 10 15Phe His Glu Thr Glu Arg Ile Ala Ser Arg Lys Glu Val Cys Asp Asp 20 25 30Asn Ser Val Ser Thr Thr Lys His Thr Val Tyr Leu Lys Leu Glu Phe 35 40 45Pro Asn Ile Ala Thr Asp Gln His Gly Asn Val Gly His Trp Thr Ile 50 55 60Ile Tyr Asn Gln Gly Phe Glu Val Ser Ile Asn Tyr Arg Lys Tyr Phe65 70 75 80Ala Phe Ser Leu Tyr Lys Gln Val Gly Lys Gln Val Thr Ser Tyr Cys 85 90 95Asp Ser Thr Phe Pro Gly Trp Ser His Asp Val Leu Gly Asn Asn Trp 100 105 110Ala Cys Phe Lys Gly Arg Lys Val Asn Arg Gln Gln Glu Lys Ser Phe 115 120 125Asp Glu Thr Met Ile Asn Asn Gly Lys Thr His Thr Val Gln Pro Phe 130 135 140Leu Leu Glu Ser Val Pro Val Asn His Asn Leu Ile Gln Met Asn Val145 150 155 160Asn Lys Ile Asn Met Lys Gln Ser Ser Trp Lys Ala Lys Phe Tyr Pro 165 170 175His Leu Met Asn Leu Asn Thr Glu Asp Leu Ile Arg Met Ala Gly Gly 180 185 190Arg Gly Ser Ala Ile Val Asn Arg Pro Ser Thr Val Pro Ala Ser Glu 195 200 205Glu Ile Lys Glu Lys Val Arg Gln Leu Pro Glu Ser Phe Asp Trp Arg 210 215 220Asn Val Asn Gly Ile Asn Tyr Val Ser Pro Val Arg Asp Gln Gly Lys225 230 235 240Cys Gly Ser Cys Tyr Ile Phe Ser Ser Met Ala Gln Leu Glu Ala Arg 245 250 255Val Arg Ile Ala Thr Asn Asn Ser Glu Gln Pro Ile Phe Ser Thr Gln 260 265 270Glu Val Val Asp Cys Ser Lys Tyr Ser Gln Gly Cys Asp Gly Gly Phe 275 280 285Pro Tyr Leu Ile Ala Gly Lys Tyr Gly Arg Asp Tyr Gly Val Ile Ala 290 295 300Asp Glu Cys Tyr Pro Tyr Lys Gly Lys Asn Gly Lys Cys Ser Leu Pro305 310 315 320Tyr Asn Ser Thr Gly Thr Lys Cys Met Lys Arg Ser Tyr Thr Leu His 325 330 335Tyr His Tyr Val Gly Gly Tyr Tyr Gly Gly Cys Asn Glu Glu Leu Met 340 345 350Leu Leu Glu Leu Val Lys Asn Gly Pro Ile Thr Val Gly Phe Glu Val 355 360 365Tyr Asp Asp Phe Thr Ser Tyr Ser Gly Gly Ile Tyr Ser His Asp Lys 370 375 380Ser Lys Asp Gln Trp Arg Asn Gly Val His Phe Asn Pro Phe Gln Leu385 390 395 400Thr Asn His Ala Val Leu Ile Val Gly Tyr Gly Val Asp Lys Gln Ser 405 410 415Gly Glu Lys Tyr Trp Ile Val Lys Asn Ser Trp Gly Lys Asp Trp Gly 420 425 430Leu Asp Gly Tyr Phe Trp Ile Lys Arg Gly Asn Asp Glu Cys Gly Ile 435 440 445Glu Ser Leu Ala Val Ser Val Thr Pro Ile Pro 450 455312309PRTBlomia tropicalis 312Ile Lys Thr Phe Glu Gln Phe Lys Lys Val Phe Gly Lys Val Tyr Arg1 5 10 15Asn Ala Glu Glu Glu Ala Arg Arg Glu His His Phe Lys Glu Gln Leu 20 25 30Lys Trp Val Glu Glu His Asn Gly Ile Asp Gly Val Glu Tyr Ala Ile 35 40 45Asn Glu Tyr Ser Asp Met Ser Glu Gln Glu Phe Ser Phe His Leu Ser 50 55 60Gly Gly Gly Leu Asn Phe Thr Tyr Met Lys Met Glu Ala Ala Lys Glu65 70 75 80Pro Leu Ile Asn Thr Tyr Gly Ser Leu Pro Gln Asn Phe Asp Trp Arg 85 90 95Gln Lys Ala Arg Leu Thr Arg Ile Arg Gln Gln Gly Ala Cys Gly Ser 100 105 110Cys Trp Ala Phe Ala Ala Ala Gly Val Ala Glu Ser Leu Tyr Ser Ile 115 120 125Gln Lys Gln Gln Ser Ile Glu Leu Ser Glu Gln Glu Leu Val Asp Cys 130 135 140Thr Tyr Asn Arg Tyr Asp Ser Ser Tyr Gln Cys Asn Gly Cys Gly Ser145 150 155 160Gly Tyr Ser Thr Glu Ala Phe Lys Tyr Met Ile Arg Thr Gly Leu Val 165 170 175Glu Glu Arg Asn Tyr Pro Tyr Asn Met Arg Thr Gln Trp Cys Asp Pro 180 185 190Asp Val Glu Gly Gln Arg Tyr His Val Ser Gly Tyr Gln Gln Leu Arg 195 200 205Tyr Gln Ser Ser Asp Glu Asp Val Met Tyr Thr Ile Gln Gln His Gly 210 215 220Pro Val Val Ile Tyr Met His Gly Ser Asn Asn Tyr Phe Arg Asn Leu225 230 235 240Gly Asn Gly Val Leu Arg Gly Val Ala Tyr Asn Asp Ala Tyr Thr Asp 245 250 255His Ala Val Ile Leu Val Gly Trp Gly Thr Val Gln Gly Val Asp Tyr 260 265 270Trp Ile Ile Arg Asn Ser Trp Gly Thr Gly Trp Gly Asn Gly Gly Tyr 275 280 285Gly Tyr Val Glu Arg Gly His Asn Ser Leu Gly Ile Asn Asn Phe Val 290 295 300Thr Tyr Ala Thr Leu305313260PRTBlomia tropicalis 313Ser Leu Thr Asn Lys Lys Tyr Asp Phe Ser Gly Lys Val Ala Leu Val1 5 10 15Thr Gly Ser Ser Ser Gly Ile Gly Ala Ala Ile Ala Ile Gln Phe Ala 20 25 30Gln Tyr Gly Ala Lys Val Thr Ile Thr Gly Arg Asn Ala Glu Asn Leu 35 40 45Asp Lys Ile Ala Lys Lys Ile Ala Glu Val Ser Asn Gly Val Glu Ala 50 55 60Leu Gln Ile Ile Gly Asp Leu Thr Ile Asp Asp Ser Leu Pro Lys Arg65 70 75 80Leu Ile Asp Glu Thr Val Thr Lys Phe Gly Arg Leu Asp Phe Leu Val 85 90 95Asn Asn Ala Gly Gly Ala Thr Pro Gln Gly Thr Leu Ala Ser Pro Asp 100 105 110Leu Leu Lys Gly Phe Asp Asp Val Phe Lys Leu Asn Val Arg Ser Val 115 120 125Ile Glu Leu Thr Gln Leu Ala Met Pro His Leu Glu Lys Thr Lys Gly 130 135

140Asn Ile Ile Asn Ile Ser Ser Val Ala Ser Ile Lys Pro Tyr Met Val145 150 155 160Val Tyr Ser Ser Ser Lys Ala Ala Leu Asp Met Ile Thr Lys Thr Ser 165 170 175Ala Leu Glu Leu Gly Pro Lys Gly Ile Arg Val Asn Ser Ile Asn Pro 180 185 190Gly Pro Val Val Thr Ala Phe Gly Arg Ser Met Gly Val Asp Pro Ser 195 200 205His His Lys Lys Met Phe Asp Ser Phe Glu Lys Gln Met Leu Met Glu 210 215 220Arg Val Gly Gln Pro Glu Asp Ile Ala Asn Leu Ala Ser Phe Leu Ala225 230 235 240Ser Asp Asp Ala Ile Asn Ile Thr Gly Ser Ile Met Val Asn Asp Ser 245 250 255Gly Cys Leu Leu 260314150PRTBlomia tropicalis 314Lys Ala Val Val Val Leu Lys Gly Asp Ser Pro Val Ser Gly Thr Ile1 5 10 15Phe Phe Glu Gln Lys Asp Asn Gly Pro Val Ser Val Thr Gly Thr Val 20 25 30Asn Gly Leu Thr Ala Gly Asp His Gly Phe His Val His Glu Phe Gly 35 40 45Asp Asn Thr Asn Gly Cys Thr Ser Ala Gly Ala His Phe Asn Pro Phe 50 55 60Gly Lys Thr His Gly Ala Pro Ala Asp Gln Glu Arg His Val Gly Asp65 70 75 80Leu Gly Asn Val Thr Ala Asp Ala Asn Gly Val Ala Asn Val Asn Ile 85 90 95Gln Asp Ser Leu Ile Thr Leu Glu Gly Ala Asn Thr Ile Val Gly Arg 100 105 110Ser Leu Val Val His Ala Asp Pro Asp Asp Leu Gly Arg Gly Gly His 115 120 125Glu Leu Ser Lys Thr Thr Gly Asn Ala Gly Gly Arg Val Ala Cys Gly 130 135 140Val Ile Gly Leu Thr Lys145 150315137PRTBlomia tropicalis 315Gln Ala Met Ala Gly Gly His Glu Ile Val Thr Ala Ala Arg Ser Gln1 5 10 15Leu Gly Val Pro Tyr Ser Trp Gly Gly Gly Asn Trp Ala Gly Lys Ser 20 25 30Lys Gly Ile Asp Ser Gly Ala His Thr Val Gly Phe Asp Cys Ser Gly 35 40 45Leu Ala Gln Tyr Ala Val Tyr His Gly Thr His Lys Lys Ile Ala Arg 50 55 60Val Ala Ser Ala Gln Tyr Ala Asp His Gln Cys His His Val Pro Tyr65 70 75 80Ala Gln His Leu Pro Gly Asp Leu Val Phe Phe Asn Asp Gly Gly Ser 85 90 95Ile His His Val Ala Ile Ile Ser Gly Lys Asn Thr Met Ile His Ala 100 105 110Pro His Thr Gly Asp His Val Arg Glu Ala Ala Val Tyr Val Lys Gly 115 120 125Arg Met Ser Thr Val Gln Arg Cys Phe 130 135316233PRTBlomia tropicalis 316Met Ser Lys Pro Thr Leu Tyr Tyr Met Trp Glu Ser Pro Pro Cys Cys1 5 10 15Thr Val Ile Ala Ile Ala Arg Ile Leu Asn Ile Glu Leu Asp Met Lys 20 25 30His Val Asp Leu Thr Lys Lys Asp Gln Asn Asn Pro Glu Phe Lys Lys 35 40 45Ile Asn Pro Phe Ala Ile Val Pro Thr Phe Val Glu Thr Asp Gly Tyr 50 55 60Thr Leu Trp Glu Ser Arg Ala Ile Ser Thr Tyr Leu Val Gln Ser Arg65 70 75 80Ser Pro Asp Ser Thr Leu Tyr Pro Gly Ser Asp Leu Lys Lys Arg Ser 85 90 95Thr Ile Asp Lys Phe Leu Gln Tyr Asp Leu Gly Thr Phe Asn Arg Ala 100 105 110Ile Tyr Asp Val Val Ser Glu Ile Phe Lys Ser Gly Lys Leu Asn Glu 115 120 125Gln Asn Ile Pro Arg Leu Gly Glu Val Leu Lys Thr Leu Glu Glu Thr 130 135 140Leu Ala Ala Asn Asn Glu Ser Asn Gly Gly Pro Phe Ile Thr Gly Asp145 150 155 160Asp Gln Leu Thr Ile Ala Asp Ile Ser Met His Phe Ser Trp Thr Leu 165 170 175Leu Ser Leu Leu Pro Glu Arg Leu Ile Asp Gln Ser Ser Tyr Pro Thr 180 185 190Ile Arg Ala Trp Asn Gln Ala Val Ile Gln Ala Leu Lys Pro Tyr Asn 195 200 205Arg Asp Gln Lys Phe Thr Glu Ala Gln Arg Arg Leu Lys Ala Phe Ile 210 215 220Thr Met Met Ile Glu Ser Ala Lys Asn225 230317252PRTBlomia tropicalis 317Asn Trp Gln Leu Val Trp Ser Asp Glu Phe Asn Gly Asn Gly Leu Asp1 5 10 15Glu Asn Asn Trp Asn Tyr Gln Thr Gly Cys Ser Gln Gln Asn Asp Glu 20 25 30Leu Glu Cys Tyr Thr Ser His Arg His Glu Asn Val Arg Val Glu Asn 35 40 45Gly His Leu Val Ile Glu Ala Arg Pro Glu Glu Tyr Gln Gly His His 50 55 60Phe Thr Ser Gly Arg Leu His Gly Lys Lys Ala Trp Ala Tyr Gly Lys65 70 75 80Phe Glu Ala Arg Ala Lys Met Pro Ser Gly His His Leu Trp Pro Ala 85 90 95Ile Trp Met Met Pro Arg Asp Ser Lys Tyr Gly Gly Trp Ala Ala Ser 100 105 110Gly Glu Ile Asp Ile Leu Glu Leu Arg Gly Asp Lys Pro His Glu Ile 115 120 125Val Gly Thr Ile His Tyr Gly Gly Ser Trp Pro Asn Asn Ile Tyr His 130 135 140Gly Ser Gly Glu Arg Tyr Tyr Gln Gln Asp Phe Ser Gln Asp Tyr His145 150 155 160Thr Phe Ala Val Glu Trp Asp Gln Lys Glu Ile Arg Trp Tyr Val Asp 165 170 175Gly Gln His Tyr His Thr Glu Asn Ile Asp Arg Asn Met Trp Ser Gly 180 185 190Arg Gly Asn Asn Pro Tyr His Lys Asn Gly Glu Pro Phe Asp Gln Pro 195 200 205Phe Tyr Trp Ile Leu Asn Val Ala Val Gly Gly Asn Phe Phe Gly Pro 210 215 220Gly Pro Tyr Val Ser Pro Ala Glu Ala Arg Asn Trp His Lys Arg Thr225 230 235 240Met Glu Val Asp Tyr Val Arg Val Tyr Gln Trp Arg 245 250318187PRTBlomia tropicalis 318Met Ser Ile Ser Ala His Gly Gly Gly Leu Ile Asn Gly Ile Ala Gly1 5 10 15Met Glu Asn Lys Phe Thr Val Phe Thr Ser Gly Lys Pro Val Ser Gly 20 25 30Leu Thr Val Ala Phe Glu Gly Pro Thr Lys Pro Asp Ile Asn Phe Asn 35 40 45Ser Ala Lys Asp Gly Ser Val Asp Val Ser Tyr Thr Pro Lys Ala Gly 50 55 60Gly Met Tyr Lys Ile His Ile Lys Tyr Asp Gly Lys Glu Ile Ile Gly65 70 75 80Ser Pro Phe Lys Thr Asn Ile Thr Gly Asp Glu Ala Thr His Arg Lys 85 90 95Leu Thr Glu Lys Val Lys Val Gly Gly Pro Asn Val Ser Thr Gly Lys 100 105 110Ala Asn Ala Asp Asn Glu Leu Thr Ile Asp Cys Lys Glu Ala Gly Ile 115 120 125Thr Gly Gly Ile Ser Phe Ala Met Glu Gly Pro Ala Lys Val Glu Val 130 135 140Ser Phe Arg Asn Asn Asn Asp Gly Thr Ile Thr Val Val Tyr Lys Pro145 150 155 160Pro Gln Asn Gly Asp Tyr Lys Leu His Leu Lys Phe Asn Asp Ile His 165 170 175Leu Pro Gly Ser Pro Phe Pro Ile Val Val Ser 180 185319125PRTArtificial sequeneSynthetic sequencemisc_feature(111)..(111)Xaa is serine, alanine, or 2-aminobutyric acid 319Gly Lys Tyr Gln Leu Glu Ser Ser Glu Asn Phe Asp Glu Phe Leu Lys1 5 10 15Glu Leu Gly Val Asn Phe Ile Leu Arg Asn Leu Ala Lys Thr Ser Lys 20 25 30Pro Thr Ile Glu Ile Thr Leu Asp Gly Asp Thr Tyr Thr Ile Lys Thr 35 40 45Ile Thr Thr Leu Lys Thr Ser Val Ile Thr Phe Lys Ile Gly Glu Glu 50 55 60Phe Glu Glu Ser Arg Met Asp Gly Lys Thr Val Lys Thr Val Ile Thr65 70 75 80Gln Glu Gly Asp Lys Leu Ile Gln Val Gln Gln Gly Asp Lys Glu Val 85 90 95Lys Ile Val Arg Glu Phe Thr Glu Thr His Leu Thr Thr Ile Xaa Thr 100 105 110Val Gly Glu Ile Thr Ser Thr Arg Val Tyr Lys Arg Val 115 120 125320363PRTArtificial sequeneSynthetic sequencemisc_feature(134)..(134)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(142)..(142)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(149)..(149)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(176)..(177)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(201)..(201)Xaa is serine, alanine, or 2-aminobutyric acid 320Met Ser Ile Ile Gln Asn Leu Pro Ala Asp Val Gln Glu Glu Leu Arg1 5 10 15Lys Thr Ala Asn Ala Ile Val Thr Pro Gly Lys Gly Ile Leu Ala Ala 20 25 30Asp Glu Ser Thr Gly Thr Ile Gly Lys Arg Phe Ala Asp Ile Asn Val 35 40 45Glu Asn Val Glu Asn Asn Arg Arg Thr Tyr Arg Asp Leu Leu Phe Ser 50 55 60Ala Pro Asp Glu Val Asn Asn Tyr Ile Ser Gly Val Ile Leu Phe Asp65 70 75 80Glu Thr Val Tyr Gln Lys Asn Ala Ala Gly Val Pro Phe Pro Gln Val 85 90 95Leu Ala Lys Arg Gly Ile Ile Pro Gly Ile Lys Val Asp Thr Gly Val 100 105 110Val Val Leu Gln Gly Thr Asn Gly Glu Ser Thr Thr Gln Gly Leu Asp 115 120 125Asn Leu Thr Lys Arg Xaa Gln Ala Tyr Tyr Glu Gln Gly Xaa Arg Phe 130 135 140Ala Lys Trp Arg Xaa Val Leu Lys Ile Gly Asp Asn Glu Pro Ser Pro145 150 155 160Leu Ala Ile Leu Glu Asn Ala Asn Val Leu Ala Arg Tyr Ala Ser Xaa 165 170 175Xaa Gln Gln Ala Arg Ile Val Pro Ile Val Glu Pro Glu Ile Leu Pro 180 185 190Asp Gly Ala His Asp Ile Glu Arg Xaa Gln Lys Val Thr Glu Lys Val 195 200 205Leu Ala Ala Val Tyr Lys Ala Leu Asn Asp His Asn Val Phe Leu Glu 210 215 220Gly Thr Leu Leu Lys Pro Asn Met Val Thr Ala Gly Gln Ser Phe Ala225 230 235 240Gly Pro Lys Pro Ser Pro Gln Glu Val Ala Arg Ala Thr Val Thr Ala 245 250 255Leu Gln Arg Thr Val Pro Ala Ala Val Pro Gly Ile Val Phe Leu Ser 260 265 270Gly Gly Gln Ser Glu Glu Glu Ala Ser Ile Asn Leu Asn Ala Ile Asn 275 280 285Gln Phe Glu Gly Lys Lys Pro Trp Ala Leu Ser Phe Ser Tyr Gly Arg 290 295 300Ala Leu Gln Ala Ser Val Leu Arg Ala Trp Gln Gly Lys Asp Glu Leu305 310 315 320Ile Ala Ala Gly Gln Lys Glu Leu Val Asn Arg Ser Lys Ala Asn Ser 325 330 335Asp Ala Ser Leu Gly Lys Tyr Ser Gly Gly Ile Val Gly Ala Ala Gly 340 345 350Glu Gln Asp Leu Phe Ile Lys Asp His Gln Tyr 355 360321973PRTArtificial sequeneSynthetic sequencemisc_feature(12)..(12)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(17)..(17)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(148)..(148)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(317)..(317)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(371)..(371)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(427)..(427)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(450)..(450)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(458)..(458)Xaa is serine, alanine, or 2-aminobutyric acid 321Val Val Ile Lys Val Glu Asn Leu Pro Ala Arg Xaa Asp Tyr Thr Lys1 5 10 15Xaa Pro Lys Ser Asp Pro Asn Lys Ile Asn Val His Leu Val Pro His 20 25 30Thr His Asp Asp Val Gly Trp Leu Lys Thr Val Glu Gln Tyr Tyr Tyr 35 40 45Gly Ser Lys Thr Tyr Tyr Gln Lys Ala Gly Val Gln Tyr Ile Leu Asp 50 55 60Ser Val Met Asn Glu Leu Ile His Asn Lys Glu Arg Lys Phe Ile Tyr65 70 75 80Val Glu Thr Ala Phe Phe Trp Lys Trp Trp Met Glu Gln Asp Tyr Gly 85 90 95Met Arg Asn Ile Val Lys Glu Leu Val Glu Thr Gly Gln Leu Glu Phe 100 105 110Ile Asn Ala Gly Trp Ser Met Asn Asp Glu Ala Ser Thr His Tyr Asn 115 120 125Ser Ile Ile Asp Gln Met Ser Trp Gly Phe Tyr Arg Leu Gln Thr Thr 130 135 140Phe Gly Arg Xaa Gly Val Pro Lys Val Ala Trp Gln Ile Asp Pro Phe145 150 155 160Gly His Ser Lys Glu Gln Ala Ala Leu Phe Ala Leu Met Asn Phe Asp 165 170 175Ala Leu Phe Phe Ala Arg Glu Asp Trp Gln Glu Gln Ser His Arg Arg 180 185 190Lys Asn Arg Thr Leu Glu His Val Trp Gln Ala Ser Ser Asp Leu Gly 195 200 205Lys Ser Ala Asp Leu Phe Thr Gly Met Met Asn Phe Gly Tyr Gly Pro 210 215 220Pro Gln Gly Phe Asn Trp Asp Leu Val Gly Gly Ala Asp Glu Pro Val225 230 235 240Ile Asp Asp Pro Glu Ser Asp Glu Tyr Asn Val Pro Arg Arg Val Lys 245 250 255Glu Leu Ile Asp Leu Ala Lys Thr Tyr Gln Lys Tyr Tyr Ala Thr Asn 260 265 270Asn Val Met Phe Pro Met Gly Thr Asp Phe Gln Tyr Gln Asp Ala His 275 280 285Ile Tyr Phe Lys Asn Met Asp Lys Leu Ile Lys Tyr Val Asn Glu Asn 290 295 300Ser Thr Glu Val Asn Ile Phe Tyr Ser Thr Pro Ser Xaa Tyr Ala Lys305 310 315 320Ser Leu Lys Asp Ser Gly Lys Thr Phe Thr Ala Lys Asn Asp Asp Tyr 325 330 335Phe Pro Tyr Ala Ser Asp Pro His Ser Tyr Trp Thr Gly Tyr Phe Thr 340 345 350Ser Arg Pro Ala Ile Lys Arg Phe Glu Arg Val Gly Asn Asn Tyr Leu 355 360 365Gln Val Xaa Lys Gln Met Asp Thr Tyr Thr Gly His Gln Ala Thr Arg 370 375 380Asp Arg His Thr Thr Lys Leu Arg Glu Ile Met Gly Val Met Gln His385 390 395 400His Asp Ala Val Ser Gly Thr Glu Lys Gln His Val Ala Phe Asn Tyr 405 410 415Ala Lys His Leu Gln Ser Gly Ile Glu Ser Xaa Arg Lys Val Ile Ser 420 425 430Glu Ala Tyr Gln Leu Leu Gln His Pro His Thr Lys Thr Val Gln Thr 435 440 445Phe Xaa Asp Tyr Leu Asn Ile Ser Ser Xaa Ala Ile Thr Glu Ser Gly 450 455 460Gln Asn Phe Val Val Asn Ile Tyr Asn Pro Leu Ser Lys Thr Leu Lys465 470 475 480Asn His Pro Ile Arg Leu Pro Ile Asn Ser Asp Lys Tyr Tyr Asn Val 485 490 495Val Asp Asp Glu Gly Lys Ser Val Tyr Ser Glu Leu Thr Phe Ile Pro 500 505 510Glu Tyr Val Gln Ala Ile Pro Glu Arg Thr Thr Asn Ala Thr Thr Asp 515 520 525Leu Val Phe Leu Ala Ser Ile Pro Pro Leu Gly Tyr Ala Ser Tyr Phe 530 535 540Val Gln Ala Thr Thr Thr Lys Ser Pro Asp Ser Ala Asn Ala Val Thr545 550 555 560Val Thr Lys Ile Thr Asn Glu Thr Arg Leu Ser Ser Gly Asn Phe Ser 565 570 575Val Val Phe Asp Ser Thr Gly Ala Leu Ser Lys Val Glu Leu Pro Ser 580 585 590Gly Glu Ser Ile Pro Phe Lys Asn Glu Phe Arg Tyr Tyr Asn Gly Ala 595 600 605Ala Asp Asn Ile Arg Ala Ser Gly Ala Tyr Ile Phe Arg Pro Lys Glu 610 615 620Gln Gln Thr Phe Pro Phe Ala Lys Leu Val Ser Ala Asn Leu Leu Thr625 630 635 640Arg Thr Ser Ser Gly Gly Ile Val His Glu Val His Gln Lys Phe Asp 645 650 655Ser Asn Val Glu Gln Val Ile Arg Val Leu Pro Asp Ser Asp Ser Ile 660 665 670Glu Phe Glu Tyr Val Val Gly Pro Ile Pro Val Lys Asp Gly Ile Gly 675 680 685Lys Glu Val Val Leu Thr Tyr Glu Thr Asp Phe Lys Asn Asn Lys Thr 690 695 700Phe Tyr Thr Asp Ala Asn Gly Arg Gln Met Met Lys Arg Lys Trp Asp705 710 715 720Tyr Arg Pro Glu Phe Lys Met Glu Val Thr Glu Pro Ile Ser Gly Asn 725

730 735Tyr Tyr Pro Ile Asn Ser Arg Ile Tyr Leu Gln Asp Glu Lys Lys Gly 740 745 750Met Gln Met Thr Ile Leu Asn Asp Arg Ser Gln Gly Gly Thr Ser Pro 755 760 765Arg Asp Gly Val Ile Glu Ile Met Val His Arg Arg Leu Leu His Asp 770 775 780Asp Gly Phe Gly Val Gly Glu Ala Leu Asn Glu Pro Gly Val Asp Asn785 790 795 800Lys Gly Leu Ile Ile Arg Gly Arg His Leu Val Gln Phe Ser Asp Ile 805 810 815Lys Thr Ala Ala Ser Lys His Arg Pro Lys Ala Gln Gln Leu Phe Met 820 825 830Ala Pro Val Leu Ser Phe Val Pro Asp Val Ser Asp Tyr Glu Thr Tyr 835 840 845Lys Arg Ser His Leu Thr Lys Tyr Ser Ala Leu Ile Asn Pro Leu Pro 850 855 860Glu Gln Ile His Leu Leu Thr Leu Glu Arg Trp Met Glu Gly His Phe865 870 875 880Leu Leu Arg Leu Glu His Tyr Phe Gln Thr Asn Glu Asp Ala Glu Leu 885 890 895Ser Lys Pro Val Thr Leu Asn Leu Lys His Met Phe Lys Ser Phe Lys 900 905 910Ile Phe Glu Ala Glu Glu Leu Thr Leu Gly Gly Asn Gln Pro Ile Phe 915 920 925Glu Thr Lys His Arg Met Lys Phe Asn Tyr Ile Pro Val Glu Asn Val 930 935 940Thr Glu Pro Pro Glu His Ser Phe Asp Pro Thr Lys Leu Glu Val Lys945 950 955 960Leu Tyr Pro Met Gln Ile Arg Thr Phe Ser Val Arg Val 965 970322889PRTArtificial sequeneSynthetic sequencemisc_feature(2)..(2)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(13)..(13)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(24)..(24)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(29)..(30)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(58)..(58)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(382)..(382)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(473)..(473)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(501)..(501)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(590)..(590)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(601)..(601)Xaa is serine, alanine, or 2-aminobutyric acid 322Gln Xaa Met Ala Ile Pro Pro Asn Ser Arg Ile Asp Xaa Asn Pro Asp1 5 10 15Pro Pro Ile Ser Ala Glu Val Xaa Gln Ser Arg Gly Xaa Xaa Trp Met 20 25 30Pro Ser Ser Asn Glu Ser Ser Glu Asn Met Asn Leu Leu Lys Lys Asn 35 40 45Val Leu Pro Pro Leu Asn Val Pro Tyr Xaa Phe Phe Gly Ser Asp Tyr 50 55 60His Gly Tyr Asn Val Ser Asn Val Gln Thr Ile Asn Asp Asn Gln Lys65 70 75 80Val Ile Asn Leu Gln Arg Ile Arg Asp Ser Gly Phe Val Asn Asp Val 85 90 95Lys Asn Val Arg Ile Gln Ile Asp Glu Leu Ser Ser Asn Val Leu Arg 100 105 110Ile Lys Met Ile Asp Ser Asp Ser Ser Arg Tyr Glu Val Pro Ile Pro 115 120 125Val Leu Asn Leu Pro Lys Arg Asn Glu Val Leu Glu Ser Leu Asn Glu 130 135 140Lys Met Tyr Gln Val Glu Met Asn Ser Thr Asp Phe Met Leu Thr Val145 150 155 160Tyr Arg Ala Lys Thr Lys Ala Ile Val Phe Asn Val Asn Leu Gly Gln 165 170 175Leu Ile Tyr Ser Asn Gln Phe Ile Gln Ile Thr Asn Lys Leu Ala Ser 180 185 190Asn Phe Ile Phe Gly Ile Gly Glu Asn Arg Glu Ser Phe Arg Lys Leu 195 200 205Thr Asn Trp Lys Arg Tyr Thr Leu Phe Ala Arg Asp Gln Trp Pro Val 210 215 220Pro Asp Arg Ala Leu Tyr Gly Ser His Pro Phe Tyr Leu Ala Thr Glu225 230 235 240Ser Asp Asn Ser Ser His Gly Val Phe Leu Phe Asn Ser Asn Ala Met 245 250 255Asp Ile Ile Thr Gln Pro Met Pro Ala Ile Thr Tyr Arg Thr Ile Gly 260 265 270Gly Ile Leu Asp Phe Phe Leu Phe Leu Gly Pro Thr Ser Glu Asn Val 275 280 285Ile Glu Gln Tyr His Gln Leu Ile Gly Leu Pro Thr Met Pro Ala Tyr 290 295 300Trp Thr Leu Gly Phe His Leu Ser Arg Tyr Gly Tyr Arg Asn Leu Ser305 310 315 320Asn Leu Glu Lys Thr Phe Arg Arg Thr Arg Lys Ala Glu Ile Pro Phe 325 330 335Asp Val Gln Trp Thr Asp Ile Asp Met Phe Asp Ser Asn Asn Asp Phe 340 345 350Thr Tyr Asp Arg Lys Arg Phe Asp Gly Leu Pro Lys Phe Ile Glu His 355 360 365Leu His Ser Ile Asn Met Arg Phe Val Pro Met Phe Asp Xaa Gly Ile 370 375 380Ser Ser Gly Glu His Pro Pro Gln Ser Tyr Leu Pro Tyr Lys Met Gly385 390 395 400Leu Glu Met Asn Val Phe Val Arg Asn Gly Thr Asn Gln Pro Phe Glu 405 410 415Gly Lys Val Trp Asn Ser Lys Ser Thr Val Trp Pro Asp Phe Thr His 420 425 430Pro Asn Ala Thr Lys Tyr Trp Thr Arg Gln Phe Ala Glu Tyr His Lys 435 440 445Thr Ile Gln Phe Asp Gly Ala Trp Ile Asp Met Asn Glu Pro Ser Asn 450 455 460Phe Leu Asp Gly Ala Phe Asn Gly Xaa Pro Thr Asn Ser Thr Leu Glu465 470 475 480Thr Pro Gln Tyr Thr Pro Gly Met Val Glu Asp Ser Leu Thr Leu Asn 485 490 495His Lys Thr Leu Xaa Met Ser Ala Arg His Ser Ile Gly Leu His Tyr 500 505 510Asn Leu His Asn Leu Tyr Gly Ile Ser Glu Ala Ile Val Thr Lys Ser 515 520 525Ala Leu Glu Ser Val Leu Lys Arg Arg Ser Phe Ile Leu Ser Arg Ser 530 535 540Thr Ala Pro Gly His Gly His Phe Ala Ala His Trp Asp Gly Asp Ile545 550 555 560Leu Ser Asp Trp Pro Ser Met Lys Trp Ser Ile Ser Ser Ile Leu Asn 565 570 575Phe Asn Ile Phe Gly Val Pro Leu Ile Gly Ala Asp Ile Xaa Gly Phe 580 585 590Asn Gly Asn Thr Thr Ile Glu Leu Xaa Ala Arg Trp His Gln Leu Gly 595 600 605Ala Phe Tyr Thr Phe Val Arg Asn His Asn Thr Asp Asn Ala Ile Asp 610 615 620Gln Asp Pro Val Ala Leu Gly Pro Leu Val Val Lys Ala Ala Lys Asn625 630 635 640Ala Leu Lys Leu Arg Tyr Ala Leu Leu Pro Tyr Leu Tyr Thr Gln Phe 645 650 655Tyr Arg Val His Arg Lys Gly Gly Thr Ile Leu Arg Pro Leu Phe Phe 660 665 670Glu Phe Val His Asp Gln Val Val Leu Glu Ile Glu Thr Gln Phe Met 675 680 685Trp Gly Ser Ser Ile Met Val Ala Pro Ala Leu Ser Ile Asn Glu Thr 690 695 700Glu Thr Ser Val Tyr Phe Pro Ser Gly Thr Trp Phe His Ser Tyr Asn705 710 715 720Phe Thr Arg Ile Asn Thr Ile Gly Lys Phe Leu Pro Gln Leu Ala Ser 725 730 735Phe Asp Tyr Pro Asn Val Tyr Phe Arg Ala Gly Ser Ile Ile Pro Thr 740 745 750Leu Arg Pro Met Leu Thr Thr Asp Glu Thr His Ser Gly Asn Phe Thr 755 760 765Leu Leu Val Ala Leu Ser Asn Glu Asn Gly His Ala Glu Gly Asp Leu 770 775 780Tyr Leu Asp Ser Gly Asp Gly Leu Asp Thr Glu Val Leu Gly His Tyr785 790 795 800Asn Leu Tyr Ser Phe Lys Val Glu Lys Lys Ile Leu Glu Ile Lys Ser 805 810 815Ser His Leu Gly Tyr Ser Thr Glu Gln Met Ile Asp Asn Val Leu Ile 820 825 830Leu Gly Ile Asp Lys Ser Pro Ile Glu Ile Lys Ile Asn Gly Arg Ser 835 840 845Met Lys Ser Trp Ser Tyr Ser Lys Asn Lys Ile His Ile Asn Ser Leu 850 855 860Asn Leu Pro Leu Tyr Asp Leu Lys Thr Ile Asp Lys Ser Lys Leu Ile865 870 875 880Gln Ile His Tyr Gln Ile Glu Trp Val 885323482PRTArtificial sequeneSynthetic sequencemisc_feature(2)..(2)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(79)..(79)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(95)..(95)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(114)..(114)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(119)..(119)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(177)..(177)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(280)..(280)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(326)..(326)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(331)..(332)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(369)..(369)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(374)..(374)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(383)..(383)Xaa is serine, alanine, or 2-aminobutyric acid 323Gly Xaa Phe Arg Ala Ala Val Leu Asp His Val His Gln Ser Ser Arg1 5 10 15Asn Gly Gly Gly Thr Lys Glu Asn Ile Lys Leu Asn Leu Lys Leu Tyr 20 25 30Glu Thr Ala Ala Lys Thr Ala Lys Glu Gln Gly Ala Asp Ile Ile Val 35 40 45Phe Pro Glu Asn Gly Ile Val Tyr Gly Ile Gly Ser Arg Ala Asn Ala 50 55 60Leu Lys Tyr Gly Glu Ile Leu Pro Glu Ser Lys Thr Ser Met Xaa Thr65 70 75 80Asp Ser Tyr Ala Ser Ser His Pro Ile Ala Tyr Gln Leu Ala Xaa Leu 85 90 95Ala Lys Glu His Gln Met Phe Val Ala Ala Asp Met Ile Asp Val Gln 100 105 110Thr Xaa Gln Thr Lys Ser Xaa Pro Ile Asp Lys Lys Tyr Ala Phe Asn 115 120 125Thr Ala Val Leu Phe Asp Arg Asn Gly Tyr Leu Leu Gly Lys Tyr His 130 135 140Lys Met His Pro Phe Gly Glu Leu Gln Phe Asn Val Pro Pro Lys Asp145 150 155 160Glu Leu Val Val Ile Glu Thr Glu Ile Gly Arg Leu Ser Met Gln Val 165 170 175Xaa Phe Asp Leu Ile Tyr Asn Lys Pro Gly Val Val Leu Ala Ser Gln 180 185 190Asp Lys Ile Asp Thr Met Leu Phe Pro Thr Trp Trp Phe Asp Glu Leu 195 200 205Pro Phe Leu Ala Ala Ser Gln Tyr Gln Met Ser Trp Ala Phe Gly Asn 210 215 220Lys Ile Asn Leu Leu Ala Ser Asn Ile His Leu Val Ala Val Gly Ser225 230 235 240Lys Gly Ser Gly Ile Phe Ala Gly Gly His Gly Gln Phe Glu Val Ile 245 250 255Ser Glu Pro Asp Ala Lys Ala Arg Ile Leu Val Ala Thr Leu Pro Ile 260 265 270Asn Ala Arg Ser Asp Ala Gln Xaa Ser Met Asp Ser Lys Lys Ile Glu 275 280 285Val Pro Gln Met Val Pro Ile Pro Ser Asn Val Ile Tyr Asn Tyr Gln 290 295 300Met Met Asn Leu Thr Glu Asn Thr Val Lys Lys Leu Asp Pro Ser Met305 310 315 320Glu Ala Ile Ser Ala Xaa Asp Gly Gly Val Xaa Xaa Gln Leu Asn Tyr 325 330 335Gln Met Asp Gln Ser Ser Ile Lys Ser Asp Glu Glu Tyr Tyr Leu Ile 340 345 350Val Thr Asn Arg Thr Arg Pro Gly Ala Tyr Pro Trp Thr Glu Glu Tyr 355 360 365Xaa Gly Leu Val Leu Xaa Pro His Met Thr Lys Leu Asp Thr Xaa Lys 370 375 380Gln Ile Ser Ser Asn Asn Pro Leu Gln Thr Lys Phe Leu Tyr Ala Lys385 390 395 400Leu Ser Gly Glu Phe Ser Ser Glu Thr His Val Tyr Pro Ser Val Ile 405 410 415Gly Ser Glu His Lys Val Leu Pro Lys Asp Gly Gly Leu Trp Thr Tyr 420 425 430Glu Asp Glu Lys Thr Asp Val Gly Ala Lys Lys Gln Lys Phe Phe Ile 435 440 445Thr Phe Gly Asn Lys Glu Glu Arg Lys Ser Tyr Thr Ile Ser Thr Ile 450 455 460Gly Leu Tyr Gly Arg Val Tyr Ala Arg Asp Pro Pro Tyr Glu Gln Lys465 470 475 480Pro Leu324491PRTArtificial sequeneSynthetic sequencemisc_feature(11)..(11)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(37)..(37)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(308)..(308)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(372)..(372)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(444)..(444)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(462)..(462)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(477)..(477)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(490)..(490)Xaa is serine, alanine, or 2-aminobutyric acid 324Asp Arg Asn Lys Leu Pro His Lys Val Val Xaa Tyr Trp Gly Thr Trp1 5 10 15Ala Phe Tyr Arg Pro Gly Ser Asp Gly Lys Phe Glu Ala Glu Asn Ile 20 25 30Asn Pro Asn Leu Xaa Thr His Ile Asn Tyr Gly Phe Ala Lys Leu Val 35 40 45Gly Asn Lys Ile Ala Leu Phe Asp Pro Asp Leu Asp Thr Gly Asp Glu 50 55 60Asp Trp Ala Ser Gly Leu Thr Trp Gly His Gly Met Ile Arg Arg Leu65 70 75 80Asn Glu Leu Arg Lys Tyr Asn Lys Asn Leu Ser Thr Leu Ile Ser Ile 85 90 95Gly Gly Trp Asn Glu Gly Ser Asn Lys Tyr Ser Thr Met Val Ser Thr 100 105 110Ala Gly Gly Arg Ser Glu Phe Val Lys Ser Val Ile Glu Phe Leu Gln 115 120 125Lys Tyr Glu Phe Asp Gly Leu Asp Leu Asp Trp Glu Tyr Pro Gly Met 130 135 140Ser Ala Ser Gly Asp Ala Asp Arg Lys Pro Gly Arg Glu Gln Asp Lys145 150 155 160Ala Asp Tyr Ile Glu Leu Leu Lys Glu Leu Arg Gln Ala Phe Glu Pro 165 170 175His Gly Tyr Ile Leu Ser Ala Ala Val Ser Ala Gly Ala Pro Thr Ile 180 185 190Asp Arg Ala Tyr Asn Val Pro Glu Val Ser Lys His Leu His Phe Ile 195 200 205Asn Leu Met Ala Tyr Asp Phe His Gly Gly Trp Asp Thr Lys Thr Ala 210 215 220His Asn Ala Pro Leu Tyr Ala Leu Pro Gly Ala Glu Gly Ile Asp Lys225 230 235 240Glu Phe Thr Val Ser Tyr Ala Val Glu Tyr Trp Ile Ser Lys Gly Ala 245 250 255Asp Pro Lys Lys Leu Val Leu Gly Ile Pro Leu Tyr Gly Arg Thr Phe 260 265 270Thr Leu Ala Gly Pro Asn His Asp Ile Gly Ala Pro Val Thr Gly His 275 280 285Gly Gly Gln Ala Gly Pro Ile Thr Arg Leu Ile Gly Met Leu Gly Tyr 290 295 300Asn Glu Ile Xaa Ser Met Val Lys Asn Gly Trp Glu Ile His Trp Asn305 310 315 320Asp Ile Gln Gln Ile Pro Tyr Ala Thr His Ala Ser Gln Trp Ile Gly 325 330 335Tyr Asp Asn Glu Lys Ser Ile Glu Lys Lys Leu Asp Tyr Val His Gln 340 345 350Lys Asn Leu Gly Gly Gly Met Val Trp Ser Ile Asp Thr Asp Asp Phe 355 360 365Ser Gly His Xaa Gly Val Lys Tyr Pro Leu Leu Lys Thr Ile Ser Arg 370 375 380Arg Leu Asn Asn Ile Asp Gly Pro Asp Val Val Ile Pro Arg Thr His385 390 395 400Ala Thr Thr Pro His Pro Asp Asp His Asp His Thr Thr Lys Arg Pro 405 410 415Asp Asp Pro His Thr Asp Pro His Thr Glu Pro His His Asp Lys Thr 420 425 430Thr Ser Ala Pro Asn Pro Asp Gly Lys Phe Gln Xaa His Ser Thr Gly 435 440 445Phe Phe Lys Asp Pro Ser Asp Pro Arg Lys Phe His Gln Xaa Val Asp 450 455 460Ile Gly Asn Gly Lys Leu Lys Asp Tyr Glu Phe Asn Xaa Pro Leu Gly465 470 475 480Ser His Tyr Asp Glu Gln Leu His Val Xaa Val 485 490325459PRTArtificial sequeneSynthetic sequencemisc_feature(6)..(6)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(30)..(30)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(96)..(96)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(114)..(114)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(241)..(241)Xaa is serine, alanine, or 2-aminobutyric

acidmisc_feature(244)..(244)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(277)..(277)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(284)..(284)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(307)..(307)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(317)..(317)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(328)..(328)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(347)..(347)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(446)..(446)Xaa is serine, alanine, or 2-aminobutyric acid 325Asp Thr Pro Ala Asn Xaa Thr Tyr Glu Asp Ile Arg Gly Glu Trp Glu1 5 10 15Phe His Glu Thr Glu Arg Ile Ala Ser Arg Lys Glu Val Xaa Asp Asp 20 25 30Asn Ser Val Ser Thr Thr Lys His Thr Val Tyr Leu Lys Leu Glu Phe 35 40 45Pro Asn Ile Ala Thr Asp Gln His Gly Asn Val Gly His Trp Thr Ile 50 55 60Ile Tyr Asn Gln Gly Phe Glu Val Ser Ile Asn Tyr Arg Lys Tyr Phe65 70 75 80Ala Phe Ser Leu Tyr Lys Gln Val Gly Lys Gln Val Thr Ser Tyr Xaa 85 90 95Asp Ser Thr Phe Pro Gly Trp Ser His Asp Val Leu Gly Asn Asn Trp 100 105 110Ala Xaa Phe Lys Gly Arg Lys Val Asn Arg Gln Gln Glu Lys Ser Phe 115 120 125Asp Glu Thr Met Ile Asn Asn Gly Lys Thr His Thr Val Gln Pro Phe 130 135 140Leu Leu Glu Ser Val Pro Val Asn His Asn Leu Ile Gln Met Asn Val145 150 155 160Asn Lys Ile Asn Met Lys Gln Ser Ser Trp Lys Ala Lys Phe Tyr Pro 165 170 175His Leu Met Asn Leu Asn Thr Glu Asp Leu Ile Arg Met Ala Gly Gly 180 185 190Arg Gly Ser Ala Ile Val Asn Arg Pro Ser Thr Val Pro Ala Ser Glu 195 200 205Glu Ile Lys Glu Lys Val Arg Gln Leu Pro Glu Ser Phe Asp Trp Arg 210 215 220Asn Val Asn Gly Ile Asn Tyr Val Ser Pro Val Arg Asp Gln Gly Lys225 230 235 240Xaa Gly Ser Xaa Tyr Ile Phe Ser Ser Met Ala Gln Leu Glu Ala Arg 245 250 255Val Arg Ile Ala Thr Asn Asn Ser Glu Gln Pro Ile Phe Ser Thr Gln 260 265 270Glu Val Val Asp Xaa Ser Lys Tyr Ser Gln Gly Xaa Asp Gly Gly Phe 275 280 285Pro Tyr Leu Ile Ala Gly Lys Tyr Gly Arg Asp Tyr Gly Val Ile Ala 290 295 300Asp Glu Xaa Tyr Pro Tyr Lys Gly Lys Asn Gly Lys Xaa Ser Leu Pro305 310 315 320Tyr Asn Ser Thr Gly Thr Lys Xaa Met Lys Arg Ser Tyr Thr Leu His 325 330 335Tyr His Tyr Val Gly Gly Tyr Tyr Gly Gly Xaa Asn Glu Glu Leu Met 340 345 350Leu Leu Glu Leu Val Lys Asn Gly Pro Ile Thr Val Gly Phe Glu Val 355 360 365Tyr Asp Asp Phe Thr Ser Tyr Ser Gly Gly Ile Tyr Ser His Asp Lys 370 375 380Ser Lys Asp Gln Trp Arg Asn Gly Val His Phe Asn Pro Phe Gln Leu385 390 395 400Thr Asn His Ala Val Leu Ile Val Gly Tyr Gly Val Asp Lys Gln Ser 405 410 415Gly Glu Lys Tyr Trp Ile Val Lys Asn Ser Trp Gly Lys Asp Trp Gly 420 425 430Leu Asp Gly Tyr Phe Trp Ile Lys Arg Gly Asn Asp Glu Xaa Gly Ile 435 440 445Glu Ser Leu Ala Val Ser Val Thr Pro Ile Pro 450 455326309PRTArtificial sequeneSynthetic sequencemisc_feature(110)..(110)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(113)..(113)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(144)..(144)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(155)..(155)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(158)..(158)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(190)..(190)Xaa is serine, alanine, or 2-aminobutyric acid 326Ile Lys Thr Phe Glu Gln Phe Lys Lys Val Phe Gly Lys Val Tyr Arg1 5 10 15Asn Ala Glu Glu Glu Ala Arg Arg Glu His His Phe Lys Glu Gln Leu 20 25 30Lys Trp Val Glu Glu His Asn Gly Ile Asp Gly Val Glu Tyr Ala Ile 35 40 45Asn Glu Tyr Ser Asp Met Ser Glu Gln Glu Phe Ser Phe His Leu Ser 50 55 60Gly Gly Gly Leu Asn Phe Thr Tyr Met Lys Met Glu Ala Ala Lys Glu65 70 75 80Pro Leu Ile Asn Thr Tyr Gly Ser Leu Pro Gln Asn Phe Asp Trp Arg 85 90 95Gln Lys Ala Arg Leu Thr Arg Ile Arg Gln Gln Gly Ala Xaa Gly Ser 100 105 110Xaa Trp Ala Phe Ala Ala Ala Gly Val Ala Glu Ser Leu Tyr Ser Ile 115 120 125Gln Lys Gln Gln Ser Ile Glu Leu Ser Glu Gln Glu Leu Val Asp Xaa 130 135 140Thr Tyr Asn Arg Tyr Asp Ser Ser Tyr Gln Xaa Asn Gly Xaa Gly Ser145 150 155 160Gly Tyr Ser Thr Glu Ala Phe Lys Tyr Met Ile Arg Thr Gly Leu Val 165 170 175Glu Glu Arg Asn Tyr Pro Tyr Asn Met Arg Thr Gln Trp Xaa Asp Pro 180 185 190Asp Val Glu Gly Gln Arg Tyr His Val Ser Gly Tyr Gln Gln Leu Arg 195 200 205Tyr Gln Ser Ser Asp Glu Asp Val Met Tyr Thr Ile Gln Gln His Gly 210 215 220Pro Val Val Ile Tyr Met His Gly Ser Asn Asn Tyr Phe Arg Asn Leu225 230 235 240Gly Asn Gly Val Leu Arg Gly Val Ala Tyr Asn Asp Ala Tyr Thr Asp 245 250 255His Ala Val Ile Leu Val Gly Trp Gly Thr Val Gln Gly Val Asp Tyr 260 265 270Trp Ile Ile Arg Asn Ser Trp Gly Thr Gly Trp Gly Asn Gly Gly Tyr 275 280 285Gly Tyr Val Glu Arg Gly His Asn Ser Leu Gly Ile Asn Asn Phe Val 290 295 300Thr Tyr Ala Thr Leu305327260PRTArtificial sequeneSynthetic sequencemisc_feature(258)..(258)Xaa is serine, alanine, or 2-aminobutyric acid 327Ser Leu Thr Asn Lys Lys Tyr Asp Phe Ser Gly Lys Val Ala Leu Val1 5 10 15Thr Gly Ser Ser Ser Gly Ile Gly Ala Ala Ile Ala Ile Gln Phe Ala 20 25 30Gln Tyr Gly Ala Lys Val Thr Ile Thr Gly Arg Asn Ala Glu Asn Leu 35 40 45Asp Lys Ile Ala Lys Lys Ile Ala Glu Val Ser Asn Gly Val Glu Ala 50 55 60Leu Gln Ile Ile Gly Asp Leu Thr Ile Asp Asp Ser Leu Pro Lys Arg65 70 75 80Leu Ile Asp Glu Thr Val Thr Lys Phe Gly Arg Leu Asp Phe Leu Val 85 90 95Asn Asn Ala Gly Gly Ala Thr Pro Gln Gly Thr Leu Ala Ser Pro Asp 100 105 110Leu Leu Lys Gly Phe Asp Asp Val Phe Lys Leu Asn Val Arg Ser Val 115 120 125Ile Glu Leu Thr Gln Leu Ala Met Pro His Leu Glu Lys Thr Lys Gly 130 135 140Asn Ile Ile Asn Ile Ser Ser Val Ala Ser Ile Lys Pro Tyr Met Val145 150 155 160Val Tyr Ser Ser Ser Lys Ala Ala Leu Asp Met Ile Thr Lys Thr Ser 165 170 175Ala Leu Glu Leu Gly Pro Lys Gly Ile Arg Val Asn Ser Ile Asn Pro 180 185 190Gly Pro Val Val Thr Ala Phe Gly Arg Ser Met Gly Val Asp Pro Ser 195 200 205His His Lys Lys Met Phe Asp Ser Phe Glu Lys Gln Met Leu Met Glu 210 215 220Arg Val Gly Gln Pro Glu Asp Ile Ala Asn Leu Ala Ser Phe Leu Ala225 230 235 240Ser Asp Asp Ala Ile Asn Ile Thr Gly Ser Ile Met Val Asn Asp Ser 245 250 255Gly Xaa Leu Leu 260328150PRTArtificial sequeneSynthetic sequencemisc_feature(54)..(54)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(143)..(143)Xaa is serine, alanine, or 2-aminobutyric acid 328Lys Ala Val Val Val Leu Lys Gly Asp Ser Pro Val Ser Gly Thr Ile1 5 10 15Phe Phe Glu Gln Lys Asp Asn Gly Pro Val Ser Val Thr Gly Thr Val 20 25 30Asn Gly Leu Thr Ala Gly Asp His Gly Phe His Val His Glu Phe Gly 35 40 45Asp Asn Thr Asn Gly Xaa Thr Ser Ala Gly Ala His Phe Asn Pro Phe 50 55 60Gly Lys Thr His Gly Ala Pro Ala Asp Gln Glu Arg His Val Gly Asp65 70 75 80Leu Gly Asn Val Thr Ala Asp Ala Asn Gly Val Ala Asn Val Asn Ile 85 90 95Gln Asp Ser Leu Ile Thr Leu Glu Gly Ala Asn Thr Ile Val Gly Arg 100 105 110Ser Leu Val Val His Ala Asp Pro Asp Asp Leu Gly Arg Gly Gly His 115 120 125Glu Leu Ser Lys Thr Thr Gly Asn Ala Gly Gly Arg Val Ala Xaa Gly 130 135 140Val Ile Gly Leu Thr Lys145 150329137PRTArtificial sequeneSynthetic sequencemisc_feature(46)..(46)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(75)..(75)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(136)..(136)Xaa is serine, alanine, or 2-aminobutyric acid 329Gln Ala Met Ala Gly Gly His Glu Ile Val Thr Ala Ala Arg Ser Gln1 5 10 15Leu Gly Val Pro Tyr Ser Trp Gly Gly Gly Asn Trp Ala Gly Lys Ser 20 25 30Lys Gly Ile Asp Ser Gly Ala His Thr Val Gly Phe Asp Xaa Ser Gly 35 40 45Leu Ala Gln Tyr Ala Val Tyr His Gly Thr His Lys Lys Ile Ala Arg 50 55 60Val Ala Ser Ala Gln Tyr Ala Asp His Gln Xaa His His Val Pro Tyr65 70 75 80Ala Gln His Leu Pro Gly Asp Leu Val Phe Phe Asn Asp Gly Gly Ser 85 90 95Ile His His Val Ala Ile Ile Ser Gly Lys Asn Thr Met Ile His Ala 100 105 110Pro His Thr Gly Asp His Val Arg Glu Ala Ala Val Tyr Val Lys Gly 115 120 125Arg Met Ser Thr Val Gln Arg Xaa Phe 130 135330233PRTArtificial sequeneSynthetic sequencemisc_feature(15)..(16)Xaa is serine, alanine, or 2-aminobutyric acid 330Met Ser Lys Pro Thr Leu Tyr Tyr Met Trp Glu Ser Pro Pro Xaa Xaa1 5 10 15Thr Val Ile Ala Ile Ala Arg Ile Leu Asn Ile Glu Leu Asp Met Lys 20 25 30His Val Asp Leu Thr Lys Lys Asp Gln Asn Asn Pro Glu Phe Lys Lys 35 40 45Ile Asn Pro Phe Ala Ile Val Pro Thr Phe Val Glu Thr Asp Gly Tyr 50 55 60Thr Leu Trp Glu Ser Arg Ala Ile Ser Thr Tyr Leu Val Gln Ser Arg65 70 75 80Ser Pro Asp Ser Thr Leu Tyr Pro Gly Ser Asp Leu Lys Lys Arg Ser 85 90 95Thr Ile Asp Lys Phe Leu Gln Tyr Asp Leu Gly Thr Phe Asn Arg Ala 100 105 110Ile Tyr Asp Val Val Ser Glu Ile Phe Lys Ser Gly Lys Leu Asn Glu 115 120 125Gln Asn Ile Pro Arg Leu Gly Glu Val Leu Lys Thr Leu Glu Glu Thr 130 135 140Leu Ala Ala Asn Asn Glu Ser Asn Gly Gly Pro Phe Ile Thr Gly Asp145 150 155 160Asp Gln Leu Thr Ile Ala Asp Ile Ser Met His Phe Ser Trp Thr Leu 165 170 175Leu Ser Leu Leu Pro Glu Arg Leu Ile Asp Gln Ser Ser Tyr Pro Thr 180 185 190Ile Arg Ala Trp Asn Gln Ala Val Ile Gln Ala Leu Lys Pro Tyr Asn 195 200 205Arg Asp Gln Lys Phe Thr Glu Ala Gln Arg Arg Leu Lys Ala Phe Ile 210 215 220Thr Met Met Ile Glu Ser Ala Lys Asn225 230331252PRTArtificial sequeneSynthetic sequencemisc_feature(26)..(26)Xaa is serine, alanine, or 2-aminobutyric acidmisc_feature(35)..(35)Xaa is serine, alanine, or 2-aminobutyric acid 331Asn Trp Gln Leu Val Trp Ser Asp Glu Phe Asn Gly Asn Gly Leu Asp1 5 10 15Glu Asn Asn Trp Asn Tyr Gln Thr Gly Xaa Ser Gln Gln Asn Asp Glu 20 25 30Leu Glu Xaa Tyr Thr Ser His Arg His Glu Asn Val Arg Val Glu Asn 35 40 45Gly His Leu Val Ile Glu Ala Arg Pro Glu Glu Tyr Gln Gly His His 50 55 60Phe Thr Ser Gly Arg Leu His Gly Lys Lys Ala Trp Ala Tyr Gly Lys65 70 75 80Phe Glu Ala Arg Ala Lys Met Pro Ser Gly His His Leu Trp Pro Ala 85 90 95Ile Trp Met Met Pro Arg Asp Ser Lys Tyr Gly Gly Trp Ala Ala Ser 100 105 110Gly Glu Ile Asp Ile Leu Glu Leu Arg Gly Asp Lys Pro His Glu Ile 115 120 125Val Gly Thr Ile His Tyr Gly Gly Ser Trp Pro Asn Asn Ile Tyr His 130 135 140Gly Ser Gly Glu Arg Tyr Tyr Gln Gln Asp Phe Ser Gln Asp Tyr His145 150 155 160Thr Phe Ala Val Glu Trp Asp Gln Lys Glu Ile Arg Trp Tyr Val Asp 165 170 175Gly Gln His Tyr His Thr Glu Asn Ile Asp Arg Asn Met Trp Ser Gly 180 185 190Arg Gly Asn Asn Pro Tyr His Lys Asn Gly Glu Pro Phe Asp Gln Pro 195 200 205Phe Tyr Trp Ile Leu Asn Val Ala Val Gly Gly Asn Phe Phe Gly Pro 210 215 220Gly Pro Tyr Val Ser Pro Ala Glu Ala Arg Asn Trp His Lys Arg Thr225 230 235 240Met Glu Val Asp Tyr Val Arg Val Tyr Gln Trp Arg 245 250332187PRTArtificial sequeneSynthetic sequencemisc_feature(123)..(123)Xaa is serine, alanine, or 2-aminobutyric acid 332Met Ser Ile Ser Ala His Gly Gly Gly Leu Ile Asn Gly Ile Ala Gly1 5 10 15Met Glu Asn Lys Phe Thr Val Phe Thr Ser Gly Lys Pro Val Ser Gly 20 25 30Leu Thr Val Ala Phe Glu Gly Pro Thr Lys Pro Asp Ile Asn Phe Asn 35 40 45Ser Ala Lys Asp Gly Ser Val Asp Val Ser Tyr Thr Pro Lys Ala Gly 50 55 60Gly Met Tyr Lys Ile His Ile Lys Tyr Asp Gly Lys Glu Ile Ile Gly65 70 75 80Ser Pro Phe Lys Thr Asn Ile Thr Gly Asp Glu Ala Thr His Arg Lys 85 90 95Leu Thr Glu Lys Val Lys Val Gly Gly Pro Asn Val Ser Thr Gly Lys 100 105 110Ala Asn Ala Asp Asn Glu Leu Thr Ile Asp Xaa Lys Glu Ala Gly Ile 115 120 125Thr Gly Gly Ile Ser Phe Ala Met Glu Gly Pro Ala Lys Val Glu Val 130 135 140Ser Phe Arg Asn Asn Asn Asp Gly Thr Ile Thr Val Val Tyr Lys Pro145 150 155 160Pro Gln Asn Gly Asp Tyr Lys Leu His Leu Lys Phe Asn Asp Ile His 165 170 175Leu Pro Gly Ser Pro Phe Pro Ile Val Val Ser 180 185

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Patent application title: IMMUNOGENIC PROTEINS AND FRAGMENTS THEREOF FROM ALLERGENIC MITES

Inventors:
IPC8 Class: AC07K14435FI
USPC Class: 1 1
Class name:
Publication date: 2020-04-23
Patent application number: 20200123213

Abstract:

Claims:

Description:

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Patent application title: IMMUNOGENIC PROTEINS AND FRAGMENTS THEREOF FROM ALLERGENIC MITES

Inventors: IPC8 Class: AC07K14435FI USPC Class: 1 1 Class name: Publication date: 2020-04-23 Patent application number: 20200123213

Abstract:

Claims:

Description:

Inventors:
IPC8 Class: AC07K14435FI
USPC Class: 1 1
Class name:
Publication date: 2020-04-23
Patent application number: 20200123213