Antibodies for oncogenic strains of HPV and methods of their use

Abstract

vides antibodies, including polyclonal and monoclonal antibodies, that bind to E6 proteins from at least three oncogenic strains of HPV. In general, the antibodies bind to amino acids motifs that are conserved between the E6 proteins of different HPV strains, particularly HPV strains 16 and 18. The subject antibodies may be used to detect HPV E6 protein in a sample, and, accordingly, the antibodies find use in a variety of diagnostic applications, including methods of diagnosing cancer. Kits for performing the subject methods and containing the subject antibodies are also provided.

Description

CROSS-REFERENCE

[0001]This application is a continuation application of Ser. No. 12/156,013, filed May 28, 2008, which is a continuation application of Ser. No. 11/021,949, filed Dec. 23, 2004, which claims the benefit of U.S. provisional patent application Ser. No. 60/532,373, filed Dec. 23, 2003, which applications are incorporated herein by reference in their entirety.

FIELD OF INVENTION

[0002]The present invention relates to detection of oncogenic strains of human papillomavirus (HPV).

BACKGROUND OF THE INVENTION

[0003]Cervical cancer is the second most common cancer diagnosis in women and is linked to high-risk human papillomavirus infection 99.7% of the time. Currently, 12,000 new cases of invasive cervical cancer are diagnosed in US women annually, resulting in 5,000 deaths each year. Furthermore, there are approximately 400,000 cases of cervical cancer and close to 200,000 deaths annually worldwide. Human papillomaviruses (HPVs) are one of the most common causes of sexually transmitted disease in the world. Overall, 50-75% of sexually active men and women acquire genital HPV infections at some point in their lives. An estimated 5.5 million people become infected with HPV each year in the US alone, and at least 20 million are currently infected. The more than 100 different isolates of HPV have been broadly subdivided into high-risk and low-risk subtypes based on their association with cervical carcinomas or with benign cervical lesions or dysplasias.

[0004]A number of lines of evidence point to HPV infections as the etiological agents of cervical cancers. Multiple studies in the 1980's reported the presence of HPV variants in cervical dysplasias, cancer, and in cell lines derived from cervical cancer. Further research demonstrated that the E6-E7 region of the genome from oncogenic HPV 18 is selectively retained in cervical cancer cells, suggesting that HPV infection could be causative and that continued expression of the E6-E7 region is required for maintenance of the immortalized or cancerous state. Further research demonstrated that the E6-E7 genes from HPV 16 were sufficient to immortalize human keratinocytes in culture. It was also demonstrated that although E6-E7 genes from high risk HPVs could transform cell lines, the E6-E7 regions from low risk, or non-oncogenic variants such as HPV 6 and HPV 11 were unable to transform human keratinocytes. HPV 16 and 18 infection was examined by in situ hybridization and E6 protein expression by immunocytochemistry in 623 cervical tissue samples at various stages of tumor progression and found a significant correlation between histological abnormality and HPV infection.

[0005]A significant unmet need exists for early and accurate diagnosis of oncogenic HPV infection as well as for treatments directed at the causative HPV infection, preventing the development of cervical cancer by intervening earlier in disease progression. Human papillomaviruses characterized to date are associated with lesions confined to the epithelial layers of skin, or oral, pharyngeal, respiratory, and, most importantly, anogenital mucosae. Specific human papillomavirus types, including HPV 6 and 11, frequently cause benign mucosal lesions, whereas other types such as HPV 16, 18, and a host of other strains, are predominantly found in high-grade lesions and cancer. Individual types of human papillomaviruses (HPV) which infect mucosal surfaces have been implicated as the causative agents for carcinomas of the cervix, breast (Yu et al. (1999) Anticancer Res. 19:55555057-5061; Liu et al. (2001) J. Hum. Virol. 44:329-334), anus, penis, prostate (De Villiers et al. (1989) Virology 171:248:253), larynx and the buccal cavity, tonsils (Snijders et al. (1994) J. Gen. Virol. 75(Pt 10):2769-2775), nasal passage (Trujillo et al. (1996) Virus Genes 12:165-178; Wu et al. (1993) Lancet 341:522-524), skin (Trenfield et al. (1993) Australas. J. Dermatol. 34:71-78), bladder (Baithun et al. (1998) Cancer Surv. 31:17-27), head and neck squamous-cell carcinomas (Braakhuis et al. (2004) J. Natl. Cancer Inst. 96:978-980), occasional periungal carcinomas, as well as benign anogenital warts. The identification of particular HPV types is used for identifying patients with premalignant lesions who are at risk of progression to malignancy. Although visible anogenital lesions are present in some persons infected with human papillomavirus, the majority of individuals with HPV genital tract infection do not have clinically apparent disease, but analysis of cytomorphological traits present in cervical smears can be used to detect HPV infection. Papanicolaou tests are a valuable screening tool, but they miss a large proportion of HPV-infected persons due to the unfortunate false positive and false negative test results. In addition, they are not amenable to worldwide testing because interpretation of results requires trained pathologists.

[0006]HPV infection is also associated with Netherton's syndrome (Weber et al. (2001) Br. J. Dermatol. 144:1044-1049) and epidermolysis verruciformis (Rubaie et al. (1998) Int. J. Dermatol. 37:766-771). HPV can also be transmitted to a fetus by the mother (Smith et al. (2004) Sex. Transm. Dis. 31:57-62; Xu et al. (1998) Chin. Med. Sci. J. 13:29-31; Cason et al. (1998) Intervirology 41:213-218).

[0007]The detection and diagnosis of disease is a prerequisite for the treatment of disease. Numerous markers and characteristics of diseases have been identified and many are used for the diagnosis of disease. Many diseases are preceded by, and are characterized by, changes in the state of the affected cells. Changes can include the expression of pathogengenes or proteins in infected cells, changes in the expression patterns of genes or proteins in affected cells, and changes in cell morphology. The detection, diagnosis, and monitoring of diseases can be aided by the accurate assessment of these changes. Inexpensive, rapid, early and accurate detection of pathogens can allow treatment and prevention of diseases that range in effect from discomfort to death.

LITERATURE

[0008]Literature of interest includes the following references: Zozulya et al., (Genome Biology 2:0018.1-0018.12, 2001; Mombairts (Annu. Rev. Neurosci 22:487-509, 1999); Raming et al., (Nature 361: 353-356, 1993); Belluscio et al., (Neuron 20: 69-81, 1988); Ronnet et al., (Annu. Rev. Physiol. 64:189-222, 2002); Lu et al., (Traffic 4: 416-533, 2003); Buck (Cell 100:611-618, 2000); Malnic et al., (Cell 96:713-723, 1999); Firestein (Nature 413:211-218, 2001); Zhao et al., (Science 279: 237-242, 1998); Touhara et al., (Proc. Natl. Acad. Sci. 96: 4040-4045, 1999); Sklar et al., (J. Biol. Chem. 261:15538-15543, 1986); Dryer et al., (TiPS 20:413-417, 1999); Ivic et al., (J. Neurobiol. 50:56-68, 2002); Munger (2002) Front. Biosci. 7:d641-9; Glaunsinger (2000) Oncogene 19:5270-80; Gardiol (1999) Oncogene 18:5487-96; Pim (1999) Oncogene 18:7403-8; Meschede (1998) J. Clin. Microbiol. 36:475-80; Kiyono (1997) Proc. Natl. Acad. Sci. 94:11612-6; and Lee (1997) Proc. Natl. Acad. Sci. 94:6670-5; Banks (1987) J. Gen. Virol. 68:1351-1359; Fuchs et al., (Hum. Genet. 108:1-13, 2001); and Giovane et al. (1999) Journal of Molecular Recognition 12:141-152 and published US patent applications 20030143679 and 20030105285; and U.S. Pat. Nos. 6,610,511, 6,492,143 6,410,249, 6,322,794, 6,344,314, 5,415,995, 5,753,233, 5,876,723, 5,648,459, 6,391,539, 5,665,535 and 4,777,239.

SUMMARY OF THE INVENTION

[0009]The subject invention provides antibodies, including polyclonal and monoclonal antibodies, that bind to the E6 proteins from at least three different oncogenic strains of HPV. In general, the antibodies bind to amino acids motifs that are conserved between the E6 proteins of different HPV strains, particularly HPV strains 16 and 18. The subject antibodies may be used to detect HPV E6 protein in a sample, and, accordingly, the antibodies find use in a variety of diagnostic applications, including methods of diagnosing cancer. Kits for performing the subject methods and containing the subject antibodies are also provided.

[0010]In certain embodiments, the invention provides an antibody composition comprising a monoclonal antibody that specifically binds to the E6 proteins of at least three (e.g., 4, 5, 6, 7 or 8 or more, usually up to 10 or 12) different oncogenic HPV strains. The antibody composition may comprise a mixture of monoclonal antibodies that specifically bind to the E6 proteins of HPV strains 16, 18, 31, 33 and 45 (e.g., HPV strains 16, 18, 31, 33, 45, 52 and 58, HPV strains 16, 18, 31, 33, 45, 52, 58, 35 and 59 or HPV strains 16, 18, 26, 30, 31, 33, 34, 45, 51, 52, 53, 58, 59, 66, 68b, 69, 70, 73 and 82, wherein at least one of said monoclonal antibodies specifically binds to the E6 proteins of at least three different oncogenic HPV strains. In certain embodiments, the monoclonal antibody may bind to the E6 proteins of HPV strains 16 and 18, wherein said antibody binds SEQ ID NOS: 1, 3 or 5 of HPV strain 16 E6 and SEQ ID NOS: 2, 4 or 6 of HPV strain 18 E6. In certain embodiments, the monoclonal antibody binds to E6 proteins of HPV strains 16 and 45 or HPV strains 16, 18, 31, 33 and 45.

[0011]The invention also provides a method of detecting an HPV E6 protein in a sample. This methods generally involves contacting the subject antibody composition with the sample, and detecting any binding of the antibodies in the composition to the sample, wherein binding of an antibody to the sample indicates the presence of an HPV E6 protein. The sample may be suspected of containing an oncogenic strain of HPV.

[0012]The invention also provides a system for detecting the presence of an oncogenic HPV E6 polypeptide in a sample. This system generally comprises a first and a second binding partner for an oncogenic HPV E6 polypeptide, wherein the first binding partner is a PDZ domain protein and said second binding partner is an subject antibody. At least one of said binding partners is attached to a solid support.

[0013]The invention also provides a method of detecting the presence of an oncogenic HPV E6 protein in a sample. This method generally comprises: contacting a sample containing an oncogenic HPV E6 protein with a PDZ domain polypeptide; and detecting any binding of the oncogenic HPV E6 protein in said sample to said PDZ domain polypeptide using an subject antibody, wherein binding of the oncogenic HPV E6 protein to said PDZ domain polypeptide indicates the presence of an oncogenic HPV E6 protein in said sample.

[0014]The invention also provides a kit containing a subject antibody; and instructions for using the antibody to detect a HPV E6 protein. The kit may also contain a PDZ domain polypeptide.

[0015]The invention also provides a peptide of less than 15 amino acids comprising any one of the sequences set forth in Table 1.

INCORPORATION BY REFERENCE

[0016]All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

[0017]The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings of which:

[0018]FIG. 1 is an alignment of E6 amino acid sequences from various oncogenic strains of HPV. From top to bottom, the various HPV E6 amino acid sequences are set forth in the sequence listing as SEQ ID NOS: 13-32, respectively. Amino acid sequence from three other oncogenic strains of HPV (strains 34, 67 and 70) are found in the sequence listing as SEQ ID NOS: 359-361.

[0019]FIG. 2 is an alignment of E6 amino acid sequences from a subset of oncogenic strains of HPV shown in FIG. 1.

[0020]FIG. 3 is a slot western blot showing antibody reactivity with E6 protein.

[0021]FIG. 4 is graph showing cross-reactivity of F22-10D11 monoclonal antibody.

DEFINITIONS

[0022]Before the present invention is further described, it is to be understood that this invention is not limited to particular embodiments described, as such may of course vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0023]Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

[0024]Throughout this application, various publications, patents and published patent applications are cited. The disclosures of these publications, patents and published patent applications referenced in this application are hereby incorporated by reference in their entirety into the present disclosure. Citation herein by Applicant of a publication, patent, or published patent application is not an admission by Applicant of said publication, patent, or published patent application as prior art.

[0025]It must be noted that as used herein and in the appended claims, the singular forms "a", "and", and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a sample" includes a plurality of such sample, and reference to "the antibody" includes reference to one or more antibodies and equivalents thereof known to those skilled in the art, and so forth. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as "solely", "only" and the like in connection with the recitation of claim elements, or the use of a "negative" limitation.

[0026]A "biopolymer" is a polymer of one or more types of repeating units, regardless of the source. Biopolymers may be found in biological systems and particularly include polypeptides and polynucleotides, as well as such compounds containing amino acids, nucleotides, or analogs thereof. The term "polynucleotide" refers to a polymer of nucleotides, or analogs thereof, of any length, including oligonucleotides that range from 10-100 nucleotides in length and polynucleotides of greater than 100 nucleotides in length. The term "polypeptide" refers to a polymer of amino acids of any length, including peptides that range from 6-50 amino acids in length and polypeptides that are greater than about 50 amino acids in length.

[0027]In most embodiments, the terms "polypeptide" and "protein" are used interchangeably. The term "polypeptide" includes polypeptides in which the conventional backbone has been replaced with non-naturally occurring or synthetic backbones, and peptides in which one or more of the conventional amino acids have been replaced with a non-naturally occurring or synthetic amino acid capable of participating in peptide bonding interactions. The term "fusion protein" or grammatical equivalents thereof is meant a protein composed of a plurality of polypeptide components, that while typically not attached in their native state, typically are joined by their respective amino and carboxyl termini through a peptide linkage to form a single continuous polypeptide. Fusion proteins may be a combination of two, three or even four or more different proteins. The term polypeptide includes fusion proteins, including, but not limited to, fusion proteins with a heterologous amino acid sequence, fusions with heterologous and homologous leader sequences, with or without N-terminal methionine residues; immunologically tagged proteins; fusion proteins with detectable fusion partners, e.g., fusion proteins including as a fusion partner a fluorescent protein, β-galactosidase, luciferase, etc., and the like.

[0028]In general, polypeptides may be of any length, e.g., greater than 2 amino acids, greater than 4 amino acids, greater than about 10 amino acids, greater than about 20 amino acids, greater than about 50 amino acids, greater than about 100 amino acids, greater than about 300 amino acids, usually up to about 500 or 1000 or more amino acids. "Peptides" are generally greater than 2 amino acids, greater than 4 amino acids, greater than about 10 amino acids, greater than about 20 amino acids, usually up to about 50 amino acids. In some embodiments, peptides are between 5 and 30 or between 8 and 15 amino acids in length.

[0029]The term "capture agent" refers to an agent that binds an analyte through an interaction that is sufficient to permit the agent to bind and concentrate the analyte from a homogeneous mixture of different analytes. The binding interaction is typically mediated by an affinity region of the capture agent. Typical capture agents include any polypeptide, e.g., a PDZ protein, however antibodies may be employed. Capture agents usually "specifically bind" one or more analytes, e.g., an oncogenic E6 protein. Accordingly, the term "capture agent" refers to a molecule or a multi-molecular complex which can specifically bind an analyte, e.g., specifically bind an analyte for the capture agent, with a dissociation constant (K_D) of less than about 10^-6 M without binding to other targets.

[0030]The term "specific binding" refers to the ability of a capture agent to preferentially bind to a particular analyte that is present in a homogeneous mixture of different analytes. Typically, a specific binding interaction will discriminate between desirable and undesirable analytes in a sample, typically more than about 10 to 100-fold or more (e.g., more than about 1000- or 10,000-fold). Typically, the affinity between a capture agent and analyte when they are specifically bound in a capture agent/analyte complex is at least 10^-7, at least 10^-8 M, at least 10^-9 M, usually up to about 10^-10 M.

[0031]The term "capture agent/analyte complex" is a complex that results from the specific binding of a capture agent with an analyte, i.e., a "binding partner pair". A capture agent and an analyte for the capture agent will typically specifically bind to each other under "conditions suitable to for specific binding", where such conditions are those conditions (in terms of salt concentration, pH, detergent, protein concentration, temperature, etc.) which allow for binding to occur between capture agents and analytes to bind in solution. Such conditions, particularly with respect to antibodies and their antigens, are well known in the art (see, e.g., Harlow and Lane (Antibodies: A Laboratory Manual Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1989)). Conditions suitable for specific binding typically permit capture agents and target pairs that have a dissociation constant (K_D) of less than about 10^-6 M to bind to each other, but not with other capture agents or targets.

[0032]As used herein, "binding partners" and equivalents refer to pairs of molecules that can be found in a capture agent/analyte complex, i.e., exhibit specific binding with each other.

[0033]The phrase "surface-bound capture agent" refers to a capture agent that is immobilized on a surface of a solid substrate, where the substrate can have a variety of configurations, e.g., a sheet, bead, strip, or other structure, such as a plate with wells.

[0034]The term "pre-determined" refers to an element whose identity is known prior to its use. For example, a "pre-determined analyte" is an analyte whose identity is known prior to any binding to a capture agent. An element may be known by name, sequence, molecular weight, its function, or any other attribute or identifier. In some embodiments, the term "analyte of interest", i.e., an known analyte that is of interest, is used synonymously with the term "pre-determined analyte".

[0035]The terms "antibody" and "immunoglobulin" are used interchangeably herein to refer to a type capture agent that has at least an epitope binding domain of an antibody. These terms are well understood by those in the field, and refer to a protein containing one or more polypeptides that specifically binds an antigen. One form of antibody constitutes the basic structural unit of an antibody. This form is a tetramer and consists of two identical pairs of antibody chains, each pair having one light and one heavy chain. In each pair, the light and heavy chain variable regions are together responsible for binding to an antigen, and the constant regions are responsible for the antibody effector functions.

[0036]The recognized immunoglobulin polypeptides include the kappa and lambda light chains and the alpha, gamma (IgG₁, IgG₂, IgG₃, IgG₄), delta, epsilon and mu heavy chains or equivalents in other species. Full-length immunoglobulin "light chains" (of about 25 kDa or about 214 amino acids) comprise a variable region of about 110 amino acids at the NH₂-terminus and a kappa or lambda constant region at the COOH-terminus. Full-length immunoglobulin "heavy chains" (of about 50 kDa or about 446 amino acids), similarly comprise a variable region (of about 116 amino acids) and one of the aforementioned heavy chain constant regions, e.g., gamma (of about 330 amino acids).

[0037]The terms "antibodies" and "immunoglobulin" include antibodies or immunoglobulins of any isotype, fragments of antibodies which retain specific binding to antigen, including, but not limited to, Fab, Fv, scFv, and Fd fragments, chimeric antibodies, humanized antibodies, single-chain antibodies, and fusion proteins comprising an antigen-binding portion of an antibody and a non-antibody protein. The antibodies may be detectably labeled, e.g., with a radioisotope, an enzyme which generates a detectable product, a fluorescent protein, and the like. The antibodies may be further conjugated to other moieties, such as members of specific binding pairs, e.g., biotin (member of biotin-avidin specific binding pair), and the like. The antibodies may also be bound to a solid support, including, but not limited to, polystyrene plates or beads, and the like. Also encompassed by the terms are Fab', Fv, F(ab')₂, and or other antibody fragments that retain specific binding to antigen.

[0038]Antibodies may exist in a variety of other forms including, for example, Fv, Fab, and (Fab')₂, as well as bi-functional (i.e. bi-specific) hybrid antibodies (e.g., Lanzavecchia et al., Eur. J. Immunol. 17, 105 (1987)) and in single chains (e.g., Huston et al., Proc. Natl. Acad. Sci. U.S.A., 85, 5879-5883 (1988) and Bird et al., Science, 242, 423-426 (1988), which are incorporated herein by reference). (See, generally, Hood et al, Immunology, Benjamin, N.Y., 2nd ed. (1984), and Hunkapiller and Hood, Nature, 323, 15-16 (1986). Monoclonal antibodies, polyclonal antibodies, and "phage display" antibodies are well known in the art and encompassed by the term "antibodies".

[0039]The term "mixture", as used herein, refers to a combination of elements, e.g., capture agents or analytes, that are interspersed and not in any particular order. A mixture is homogeneous and not spatially separable into its different constituents. Examples of mixtures of elements include a number of different elements that are dissolved in the same aqueous solution, or a number of different elements attached to a solid support at random or in no particular order in which the different elements are not specially distinct. In other words, a mixture is not addressable. To be specific, an array of capture agents, as is commonly known in the art, is not a mixture of capture agents because the species of capture agents are spatially distinct and the array is addressable.

[0040]"Isolated" or "purified" general refers to isolation of a substance (compound, polynucleotide, protein, polypeptide, polypeptide composition) such that the substance comprises the majority percent of the sample in which it resides. Typically in a sample a substantially purified component comprises 50%, preferably 80%-85%, more preferably 90-95% of the sample. Techniques for purifying polynucleotides and polypeptides, e.g., antibodies, of interest are well-known in the art and include, for example, ion-exchange chromatography, affinity chromatography and sedimentation according to density.

[0041]The term "assessing" refers to any form of measurement, and includes determining if an element is present or not. The terms "determining", "measuring", "evaluating", "assessing" and "assaying" are used interchangeably and include both quantitative and qualitative determinations. Assessing may be relative or absolute. "Assessing the presence of" includes determining the amount of something present, as well as determining whether it is present or absent.

[0042]The term `marker" or "biological marker", as used herein, refers to a measurable or detectable entity in a biological sample. Examples or markers include nucleic acids, proteins, or chemicals that are present in biological samples. One example of a marker is the presence of viral or pathogen proteins or nucleic acids in a biological sample from a human source.

[0043]The term "sample" as used herein relates to a material or mixture of materials, typically, although not necessarily, in fluid form, i.e., aqueous, containing one or more components of interest. Samples may be derived from a variety of sources such as from food stuffs, environmental materials, a biological sample or solid, such as tissue or fluid isolated from an individual, including but not limited to, for example, plasma, serum, spinal fluid, semen, lymph fluid, the external sections of the skin, respiratory, intestinal, and genitourinary tracts, tears, saliva, milk, blood cells, tumors, organs, and also samples of in vitro cell culture constituents (including but not limited to conditioned medium resulting from the growth of cells in cell culture medium, putatively virally infected cells, recombinant cells, and cell components). The term "biological sample" is meant to distinguish between a sample in a clinical setting from a sample that may be a recombinant sample or derived from a recombinant sample.

[0044]Components in a sample are termed "analytes" herein. In many embodiments, the sample is a complex sample containing at least about 10², 5×10², 10³, 5×10³, 10⁴, 5×10⁴, 10⁵, 5×10⁵, 10⁶, 5×10⁶, 10⁷, 5×10⁷, 10⁸, 10⁹, 10¹⁹, 10¹¹, 10¹² or more species of analyte.

[0045]The term "analyte" is used herein interchangeably and refers to a known or unknown component of a sample, which will specifically bind to a capture agent if the analyte and the capture agent are members of a specific binding pair. In general, analytes are biopolymers, i.e., an oligomer or polymer such as an oligonucleotide, a peptide, a polypeptide, an antibody, or the like. In this case, an "analyte" is referenced as a moiety in a mobile phase (typically fluid), to be detected by a "capture agent" which, in some embodiments, is bound to a substrate, or in other embodiments, is in solution. However, either of the "analyte" or "capture agent" may be the one which is to be evaluated by the other (thus, either one could be an unknown mixture of analytes, e.g., polypeptides, to be evaluated by binding with the other).

[0046]A "fusion protein" or "fusion polypeptide" as used herein refers to a composite protein, i.e., a single contiguous amino acid sequence, made up of two (or more) distinct, heterologous polypeptides that are not normally fused together in a single amino acid sequence. Thus, a fusion protein can include a single amino acid sequence that contains two entirely distinct amino acid sequences or two similar or identical polypeptide sequences, provided that these sequences are not normally found together in the same configuration in a single amino acid sequence found in nature. Fusion proteins can generally be prepared using either recombinant nucleic acid methods, i.e., as a result of transcription and translation of a recombinant gene fusion product, which fusion comprises a segment encoding a polypeptide of the invention and a segment encoding a heterologous protein, or by chemical synthesis methods well known in the art.

[0047]An "oncogenic HPV strain" is an HPV strain that is known to cause cervical cancer as determined by the National Cancer Institute (NCI, 2001). "Oncogenic E6 proteins" are E6 proteins encoded by the above oncogenic HPV strains. The sequences of exemplary oncogenic E6 proteins of interest are shown in FIG. 1. The sequences of various HPV proteins are also found as database entries at NCBI's Genbank database, as follows: HPV16-E6: GI:9627100; HPV18-E6: GI:9626069; HPV31-E6: GI:9627109; HPV35-E6: GI:9627127; HPV30-E6: GI:9627320; HPV39-E6: GI:9627165; HPV45-E6: GI:9627356; HPV51-E6: GI:9627155; HPV52-E6: GI:9627370; HPV56-E6: GI:9627383; HPV59-E6: GI:9627962; HPV58-E6: GI:9626489; HPV33-E6: GI:9627118; HPV66-E6: GI:9628582; HPV68b-E6: GI:184383; HPV69-E6: GI:9634605; HPV26-E6: GI:396956; HPV53-E6: GI:9627377; HPV73: GI:1491692; HPV82: GI:9634614, HPV34 GI:396989; HPV67 GI:3228267; and HPV70 GI:1173493.

[0048]An "oncogenic E6 protein binding partner" can be any molecule that specifically binds to an oncogenic E6 protein. Suitable oncogenic E6 protein binding partners include a PDZ domain (as described below), antibodies against oncogenic E6 proteins (such as those described below); other proteins that recognize oncogenic E6 protein (e.g., p53, E6-AP or E6-BP); DNA (i.e., cruciform DNA); and other partners such as aptamers. In some embodiments, detection of more than 1 oncogenic E6 protein (e.g., all oncogenic E6 proteins, E6 proteins from HPV strains 16 and 18, or E6 proteins from HPV strains 16 and 45 etc.) is desirable, and, as such, an oncogenic E6 protein binding partner may be antibody that binds to these proteins, as described below, or a mixture of antibodies that each bind to a different proteins. As is known in the art, such binding partners may be labeled to facilitate their detection. In general, binding partner bind E6 with an binding affinity of less then 10^-5 M, e.g., less than 10^-6, less than 10^-7, less than 10^-8 M (e.g., less than 10^-9 M, 10^-10, 10^-11, etc.).

[0049]As used herein, the term "PDZ domain" refers to protein sequence of less than approximately 90 amino acids, (i.e., about 80-90, about 70-80, about 60-70 or about 50-60 amino acids), characterized by homology to the brain synaptic protein PSD-95, the Drosophila septate junction protein Discs-Large (DLG), and the epithelial tight junction protein ZO1 (ZO1). PDZ domains are also known as Discs-Large homology repeats ("DHRs") and GLGF repeats. PDZ domains generally appear to maintain a core consensus sequence (Doyle, D. A., 1996, Cell 85: 1067-76).

[0050]PDZ domains are found in diverse membrane-associated proteins including members of the MAGUK family of guanylate kinase homologs, several protein phosphatases and kinases, neuronal nitric oxide synthase, tumor suppressor proteins, and several dystrophin-associated proteins, collectively known as syntrophins.

[0051]Exemplary PDZ domain-containing proteins and PDZ domain sequences are shown in TABLE 2. The term "PDZ domain" also encompasses variants (e.g., naturally occurring variants) of the sequences (e.g., polymorphic variants, variants with conservative substitutions, and the like) and domains from alternative species (e.g. mouse, rat). Typically, PDZ domains are substantially identical to those shown in U.S. patent application Ser. Nos. 09/724,553 and 10/938,249), e.g., at least about 70%, at least about 80%, or at least about 90% amino acid residue identity when compared and aligned for maximum correspondence. It is appreciated in the art that PDZ domains can be mutated to give amino acid changes that can strengthen or weaken binding and to alter specificity, yet they remain PDZ domains (Schneider et al., 1998, Nat. Biotech. 17:170-5). Unless otherwise indicated, a reference to a particular PDZ domain (e.g. a MAGI-1 domain 2) is intended to encompass the particular PDZ domain and HPV E6-binding variants thereof. In other words, if a reference is made to a particular PDZ domain, a reference is also made to variants of that PDZ domain that bind oncogenic E6 protein of HPV, as described below. In this respect it is noted that the numbering of PDZ domains in a protein may change. For example, the MAGI-1 domain 2, as referenced herein, may be referenced as MAGI-1 domain 1 in other literature. As such, when a particular PDZ domain of a protein is referenced in this application, this reference should be understood in view of the sequence of that domain, as described herein, particularly in the sequence listing. Table 2 shows the relationship between the sequences of the sequence listing and the names and Genbank accession numbers for various domains, where appropriate. Further description of PDZ proteins, particularly a description of MAGI-1 domain 2 protein, is found in Ser. No. 10/630,590, filed Jul. 29, 2003 and published as US20040018487. This publication is incorporated by reference herein in its entirety for all purposes.

[0052]As used herein, the term "PDZ protein" refers to a naturally occurring protein containing a PDZ domain. Exemplary PDZ proteins include CASK, MPP1, DLG1, DLG2, PSD95, NeDLG, TIP-33, SYN1a, TIP-43, LDP, LIM, LIMK1, LIMK2, MPP2, NOS1, AF6, PTN-4, prIL16, 41.8 kD, KIAA0559, RGS12, KIAA0316, DVL1, TIP-40, TIAM1, MINT1, MAGI-1, MAGI-2, MAGI-3, KIAA0303, CBP, MINT3, TIP-2, KIAA0561, and TIP-1.

[0053]As used herein, the term "PL protein" or "PDZ Ligand protein" refers to a protein that forms a molecular complex with a PDZ-domain, or to a protein whose carboxy-terminus, when expressed separately from the full length protein (e.g., as a peptide fragment of 4-25 residues, e.g., 8, 10, 12, 14 or 16 residues), forms such a molecular complex. The molecular complex can be observed in vitro using a variety of assays described infra.

[0054]As used herein, a "PL sequence" refers to the amino acid sequence of the C-terminus of a PL protein (e.g., the C-terminal 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 14, 16, 20 or 25 residues) ("C-terminal PL sequence") or to an internal sequence known to bind a PDZ domain ("internal PL sequence").

[0055]As used herein, a "PL fusion protein" is a fusion protein that has a PL sequence as one domain, typically as the C-terminal domain of the fusion protein. An exemplary PL fusion protein is a tat-PL sequence fusion.

[0056]In the case of the PDZ domains described herein, a "HPV E6-binding variant" of a particular PDZ domain is a PDZ domain variant that retains HPV E6 PDZ ligand binding activity. Assays for determining whether a PDZ domain variant binds HPV E6 are described in great detail below, and guidance for identifying which amino acids to change in a specific PDZ domain to make it into a variant may be found in a variety of sources. In one example, a PDZ domain may be compared to other PDZ domains described herein and amino acids at corresponding positions may be substituted, for example. In another example, the sequence a PDZ domain of a particular PDZ protein may be compared to the sequence of an equivalent PDZ domain in an equivalent PDZ protein from another species. For example, the sequence of a PDZ domain from a human PDZ protein may be compared to the sequence of other known and equivalent PDZ domains from other species (e.g., mouse, rat, etc.) and any amino acids that are variant between the two sequences may be substituted into the human PDZ domain to make a variant of the PDZ domain. For example, the sequence of the human MAGI-1 PDZ domain 2 may be compared to equivalent MAGI-1 PDZ domains from other species (e.g. mouse Genbank gi numbers 7513782 and 28526157 or other homologous sequences) to identify amino acids that may be substituted into the human MAGI-1-PDZ domain to make a variant thereof. Such method may be applied to any of the MAGI-1 PDZ domains described herein. Minimal MAGI-PDZ domain 2 sequence is provided as SEQ ID NOS:68-76. Particular variants may have 1, up to 5, up to about 10, up to about 15, up to about 20 or up to about 30 or more, usually up to about 50 amino acid changes as compared to a sequence set forth in the sequence listing. Exemplary MAGI-1 PDZ variants include the sequences set forth in SEQ ID NOS: 76-105. In making a variant, if a GFG motif is present in a PDZ domain, in general, it should not be altered in sequence.

[0057]In general, variant PDZ domain polypeptides have a PDZ domain that has at least about 70 or 80%, usually at least about 90%, and more usually at least about 98% sequence identity with a variant PDZ domain polypeptide described herein, as measured by BLAST 2.0 using default parameters, over a region extending over the entire PDZ domain.

[0058]As used herein, a "detectable label" has the ordinary meaning in the art and refers to an atom (e.g., radionuclide), molecule (e.g., fluorescein), or complex, that is or can be used to detect (e.g., due to a physical or chemical property), indicate the presence of a molecule or to enable binding of another molecule to which it is covalently bound or otherwise associated. The term "label" also refers to covalently bound or otherwise associated molecules (e.g., a biomolecule such as an enzyme) that act on a substrate to produce a detectable atom, molecule or complex. Detectable labels suitable for use in the present invention include any composition detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical or chemical means. Labels useful in the present invention include biotin for staining with labeled streptavidin conjugate, magnetic beads (e.g., Dynabeads®), fluorescent dyes (e.g., fluorescein, Texas red, rhodamine, green fluorescent protein, enhanced green fluorescent protein, and the like), radiolabels (e.g., ³H, ¹²⁵I, ³⁵S, ¹⁴C, or ³²P), enzymes (e.g., hydrolases, particularly phosphatases such as alkaline phosphatase, esterases and glycosidases, or oxidoreductases, particularly peroxidases such as horse radish peroxidase, and others commonly used in ELISAs), substrates, cofactors, inhibitors, chemiluminescent groups, chromogenic agents, and colorimetric labels such as colloidal gold or colored glass or plastic (e.g., polystyrene, polypropylene, latex, etc.) beads. Patents disclosing such labels include U.S. Pat. Nos. 3,817,837; 3,850,752; 3,939,350; 3,996,345; 4,277,437; 4,275,149; and 4,366,241. Means of detecting such labels are well known to those of skill in the art.

[0059]As used herein, the terms "sandwich", "sandwich ELISA", "Sandwich diagnostic" and "capture ELISA" all refer to the concept of detecting a biological polypeptide with two different test agents. For example, a PDZ protein could be directly or indirectly attached to a solid support. Test sample could be passed over the surface and the PDZ protein could bind its cognate PL protein(s). A labeled antibody or alternative detection reagent could then be used to determine whether a specific PL protein had bound the PDZ protein.

[0060]By "solid phase support" or "carrier" is intended any support capable of binding polypeptide, antigen or antibody. Well-known supports or carriers, include glass, polystyrene, polypropylene, polyethylene, dextran, nylon, amylases, natural and modified celluloses, polyacrylamides, agaroses, and magnetite. The nature of the carrier can be either soluble to some extent or insoluble for the purposes of the present invention. The support material can have virtually any possible structural configuration so long as the coupled molecule is capable of binding to a PDZ domain polypeptide or an E6 antibody. Thus, the support configuration can be spherical, as in a bead, or cylindrical, as in the inside surface of a test tube, or the external surface of a rod. Alternatively, the surface can be flat, such as a sheet, culture dish, test strip, etc. Those skilled in the art will know many other suitable carriers for binding antibody, peptide or antigen, or can ascertain the same by routine experimentation.

[0061]In some embodiments "proteasome inhibitors", i.e., inhibitors of the proteasome, may be used. These inhibitors, including carbobenzoxyl-leucinyl-leuciny-1 norvalinal II (MG 115) or CBZ-LLL, can be purchased from chemical supply companies (e.g., Sigma). As a skilled person would understand, proteasome inhibitors are not protease inhibitors.

[0062]As used herein, a "plurality" of components has its usual meaning. In some embodiments, the plurality is at least 5, and often at least 25, at least 40, or at least 60 or more, usually up to about 100 or 1000.

[0063]Reference to an "amount" of a E6 protein in these contexts is not intended to require quantitative assessment, and may be either qualitative or quantitative, unless specifically indicated otherwise.

[0064]The term "non-naturally occurring" or "recombinant" means artificial or otherwise not found in nature. Recombinant cells usually contain nucleic acid that is not usually found in that cell, recombinant nucleic acid usually contain a fusion of two or more nucleic acids that is not found in nature, and a recombinant polypeptide is usually produced by a recombinant nucleic acid.

[0065]"Subject", "individual," "host" and "patient" are used interchangeably herein, to refer to any animal, e.g., mammal, human or non-human. Generally, the subject is a mammalian subject. Exemplary subjects include, but are not necessarily limited to, humans, non-human primates, mice, rats, cattle, sheep, goats, pigs, dogs, cats, birds, deer, elk, rabbit, reindeer, deer, and horses, with humans being of particular interest.

DETAILED DESCRIPTION OF THE INVENTION

[0066]While preferred embodiments of the present invention have been shown and described herein, it will be obvious to those skilled in the art that such embodiments are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention. It is intended that the following claims define the scope of the invention and that methods and structures within the scope of these claims and their equivalents be covered thereby.

[0067]The subject invention provides antibodies, including polyclonal and monoclonal antibodies, that bind to E6 proteins from at least three oncogenic strains of HPV. In general, the antibodies bind to amino acid motifs that are conserved between the E6 proteins of different HPV strains, particularly HPV strains 16 and 18. The subject antibodies may be used to detect HPV E6 protein in a sample, and, accordingly, the antibodies find use in a variety of diagnostic applications, including methods of diagnosing cancer. Kits for performing the subject methods and containing the subject antibodies are also provided.

[0068]In further describing the invention in greater detail than provided in the Summary and as informed by the Background and Definitions provided above, the subject antibodies are described first, followed by a description of methods in which the subject antibodies find use. Finally, kits for performing the subject methods are described.

[0069]Antibody Compositions

[0070]The invention provides antibodies, particularly monoclonal antibodies, that bind to E6 proteins of multiple strains of HPV. In other words, the invention provides antibodies that "recognize", i.e., specifically bind to with K_D of 10^-6 M or less, multiple E6 proteins. In other words, the subject antibodies each bind to (i.e., cross-react with) a plurality of different E6 proteins (i.e., at least 2, at least 3, at least 4, at least 5, at least 6 or at least 10, usually up to about 12, 15 or 20 or more different E6 proteins) from oncogenic, and, in certain embodiments, non-oncogenic strains of HPV. In general, the subject antibodies bind to amino acid motifs that are conserved between the E6 proteins of different HPV strains, and, accordingly, bind to E6 proteins that have this motif. In many embodiments the antibodies bind at least the E6 proteins of HPV strains 16 and 18 (e.g. the E6 proteins of HPV strains 16, 18, 31, 33 and 45; 16, 18 and 45; or, in other embodiments, the E6 proteins of all of the HPV strains listed in FIG. 1 or 2). In other embodiments, the antibodies bind to at least the E6 proteins from HPV strains 16 and 45. The subject antibodies may bind E6 protein from non-oncogenic strains of HPV (e.g., HPV strains 6 and/or 11) and, accordingly, the subject antibodies may bind to E6 proteins from oncogenic, as well as non-oncogenic, strains of HPV.

[0071]The subject antibodies may specifically bind to one of three sequence motifs found in HPV E6 proteins. These motifs are boxed in FIG. 1, and generally correspond to regions of sequence similarity between E6 proteins from different strains of HPV. In general, therefore, a subject antibody binds to peptides having the following sequence: FQDPQERPRKLPQLCTELQTTIHDI (SEQ ID NO:1) and FEDPTRRPYKLPDLCTELNTSLQDI (SEQ ID NO:2), corresponding to a first common sequence motif in the E6 proteins of HPV strains 16 and 18, respectively, LLIRCINCQKPLCPEEKQRHLDK (SEQ ID NO:3) and LLIRCLRCQKPLNPAEKLRHLNE (SEQ ID NO:4), corresponding to a second common sequence motif in the E6 proteins of HPV strains 16 and 18, respectively, or RHLDKKQRFHNIRGRWTGRCMSCC (SEQ ID NO:5) and RHLNEKRRFHNIAGHYRGQCHSCC (SEQ ID NO:6) corresponding to a third common sequence motif in the E6 proteins of HPV strains 16 and 18, respectively. If a subject antibody binds to other E6 proteins, then it usually binds to the other E6 proteins at positions equivalent to those discussed above, or boxed in FIG. 1, where "positions equivalent to" generally means a stretch of contiguous amino acids that correspond to, i.e., are aligned with, the boxed amino acids when the sequence of the other E6 proteins are with those in FIG. 1.

[0072]Accordingly, since antibodies generally recognize motifs smaller than those listed above, a subject antibody may recognize peptides that are smaller than and contained within the motifs described above. For example, a subject antibody may bind to a peptide having any 9 contiguous amino acids set forth in any one of SEQ NOS:1-6. In particular, a subject antibody may recognize the sequences RPRKLPQLCTEL (SEQ ID NO:7) and RPYKLPDLCTEL (SEQ ID NO:8), corresponding to sub-sequences of the first common sequences of E6 proteins of HPV strains 16 and 18, described above, LLIRCINCQKPL (SEQ ID NO:9) and LLIRCLRCQKPL (SEQ ID NO:10) corresponding to sub-sequences of the second common sequences of E6 proteins of HPV strains 16 and 18, as described above, or RHLDKKQRFHNI (SEQ ID NO:11) and RHLNEKRRFHNI (SEQ ID NO:12) corresponding to sub-sequences of the third common sequences of E6 proteins of HPV strains 16 and 18, as described above. Since these sub-sequences are generally conserved between different E6 proteins, as discussed above, antibodies that bind to the above-recited sequences generally bind to E6 proteins from other HPV strains.

[0073]In certain alternative embodiments, the subject antibodies will bind to E6 proteins from HPV strains 16 and 45. In general, therefore, a subject antibody binds to peptides having the following sequence: FQDPQERPRKLPQLCTELQTTIHDI (SEQ ID NO:1) and FDDPKQRPYKLPDLCTELNTSLQDV (SEQ ID NO:57), corresponding to a first common sequence motif in the E6 proteins of HPV strains 16 and 45, respectively, LLIRCINCQKPLCPEEKQRHLDK (SEQ ID NO:3) and LLIRCLRCQKPLNPAEKRRHLKD (SEQ ID NO: 58), corresponding to a second common sequence motif in the E6 proteins of HPV strains 16 and 45, respectively, or RHLDKKQRFHNIRGRWTGRCMSCC (SEQ ID NO:5) and RHLKDKRRFHSIAGQYRGQCNTCC (SEQ ID NO:59) corresponding to a third common sequence motif in the E6 proteins of HPV strains 16 and 45, respectively. If a subject antibody binds to other E6 proteins, then it usually binds to the other E6 proteins at positions equivalent to those discussed above, or boxed in FIG. 1. For example, the E6 proteins from HPV58, HPV33, HPV52, HPV31, HPV16, HPV18 and HPV45 are shown in FIG. 2, and the above-referenced motifs are boxed therein.

[0074]Accordingly, since antibodies generally recognize motifs smaller than those listed above, a subject antibody may recognize peptides that are smaller than and contained within the motifs described above. For example, a subject antibody may bind to a peptide having any 9 contiguous amino acids set forth in any one of SEQ NOS: 1, 3, 5, 57, 58 and 59. In particular, a subject antibody may recognize the sequences RPRKLPQLCTEL (SEQ ID NO:7) and RPYKLPDLCTEL (SEQ ID NO:60), corresponding to sub-sequences of the first common sequences of E6 proteins of HPV strains 16 and 45, described above, LLIRCINCQKPL (SEQ ID NO:9) and LLIRCLRCQKPL (SEQ ID NO: 61) corresponding to sub-sequences of the second common sequences of E6 proteins of HPV strains 16 and 45, as described above, or RHLDKKQRFHNI (SEQ ID NO:11) and RHLKDKRRFHSI (SEQ ID NO: 62) corresponding to sub-sequences of the third common sequences of E6 proteins of HPV strains 16 and 45, as described above. Since these sub-sequences are generally conserved between different E6 proteins, as discussed above, antibodies that bind to the above-recited sequences generally bind to E6 proteins from other HPV strains. In certain embodiments, cysteine residues can be replaced by serine residues to avoid disulfide bridge formation.

[0075]Methods for making antibodies, particular monoclonal antibodies, are well known in the art and described in various well known laboratory manuals (e.g., Harlow et al., Antibodies: A Laboratory Manual, First Edition (1988) Cold spring Harbor, N.Y.; Harlow and Lane, Using Antibodies: A Laboratory Manual, CSHL Press (1999) and Ausubel, et al., Short Protocols in Molecular Biology, 3rd ed., Wiley & Sons, (1995)). Accordingly, given the peptide sequences set forth above and in the accompanying tables, methods for making the subject antibodies do not need to be described herein in any great detail. Any fragment of a longer full-length E6 protein that contains a subject common motif (e.g., the full length protein), a full length E6 protein, or a fusion protein thereof may be used to make the subject antibodies. In certain embodiments, a full length E6 protein, a peptide containing a recited sequence, or a chemically modified (e.g., conjugated) derivative or fusion thereof (e.g., a MBP or GST fusion), may be used as an antigen. In certain embodiments, a nucleic acid encoding the polypeptide may be employed, or a mixture of different polypeptides (e.g., a mixture of E6 polypeptides, each polypeptide from a different HPV strain) may be used as an antigen (Michel (2002) Vaccine 20:A83-A88). Accordingly an antigen is mixed with an adjuvant, and a suitable non-human animal (e.g., a mouse, chicken, goat, rabbit, hamster, horse, rat or guinea pig, etc.) is immunized using standard immunization techniques (e.g., intramuscular injection) and once a specific immune response of the has been established, blood from the animal may be collected and polyclonal antisera that specifically binds to described peptides may be isolated. In many cases, cells from the spleen of the immunized animal are fused with a myeloma cell line, and, after fusion, the cells are grown in selective medium containing e.g., hypoxanthine, aminopterin, and thymidine (HAT), to select for hybridoma growth, and after 2-3 weeks, hybridoma colonies appear. Supernatants from these cultured hybridoma cells are screened for antibody secretion, usually by enzyme-linked immunosorbent assay (ELISA) or the like, and positive clones secreting monoclonal antibodies specific for the antigen can be selected and expanded according to standard procedures.

[0076]Exemplary peptides suitable for immunizations are described in Table 1. The peptides are shown as a "consensus" sequence (i.e. peptides in which one of several amino acids may exist at one or more positions) in order to indicate that any one or a mixture of different peptides that are described by the consensus could be used to make the subject antibodies. Accordingly, when a consensus sequence is described, every individual peptide that falls within the consensus should be considered explicitly described. In particular embodiments, exemplary species of peptide encompassed by the consensus sequences have a sequence found in a naturally-occurring HPV E6 protein, such as those described in FIG. 1. Such exemplary sequences can be identified as sequences starting at the amino acid positions defined by the third column of Table 1, "Starting AA" of particular HPV types "HPV type", and corresponding positions of other HPV E6 proteins (i.e., those positions that are aligned with the positions indicated in Table 1).

[0077]Accordingly, peptides having 9, 10, 11, 12, 13, 14, 15 or more, usually up to about 20 or more contiguous amino acids of any of the peptides described above may be used for immunizations. In some embodiments, a recited peptide sequence may be contained within a larger peptide that may be 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 or more, sometimes up to about 15 or 20 or more amino acids greater in size than a recited polypeptide. Accordingly, a subject peptide may be from about 8 to about 30 amino acids in length. In certain embodiments, a subject peptide is about 9-20 amino acids in length, and usually contains an amino acid sequence described above.

[0078]Accordingly, depending on the antibodies desired, a suitable animal is immunized with a subject peptide or a mixture of subject peptides (e.g., a mixture of 2, 3, 4, 5 about 6 or more, about 10 or more or about 15 or more, usually up to about 20 or 30 or more peptides described above). Antibodies are usually isolated from the animal and tested for binding to different HPV E6 proteins using standard methods (e.g., ELISA, western blot, etc.). In many embodiments, therefore, antibodies will be screened for binding to E6 proteins from HPV strains 16 and 18, HPV strains 16, 18, 31, 33 and 45, or, in certain embodiments, all of the HPV strains shown in FIG. 1 or 2, and may be others. Accordingly, antibodies that bind to, i.e., cross-react with, E6 proteins from more than one strain of HPV may be identified, and permanent cell lines producing those antibodies may be established using known methods. In other words, antibodies are usually tested for binding to more than one antigen, and those antigens are usually E6 proteins from various HPV strains, or fragments thereof. In most embodiments, the antibodies will be tested for binding to antigens in native and denatured states. Antibodies that bind to a plurality of E6 proteins have desirable binding properties, and, accordingly, find use in the subject methods.

[0079]As is well known in the art, the subject antibodies may be conjugated to a detectable label, or may be part of a signal generating system, as described above.

[0080]Accordingly, using the methods set forth above, an antibody composition for detecting a plurality of HPV E6 proteins is provided. In certain embodiments, a mixture of different antibodies that recognize at least 5, 7, 9, 12, 15, 20 or 24 different strains of HPV may be employed. The composition may contain at least one antibody that recognizes at least 3 different oncogenic E6 proteins. The composition may contain 1, 2, 3, 4, or 5 or more different antibodies, each antibody of the composition recognizing at least one (e.g., 2, 3, about 5, about 10, etc.) E6 protein. Collectively, the antibodies bind to all or a portion of the E6 proteins shown in FIG. 1, and, in certain embodiments, may also bind to non-oncogenic E6 proteins. The antibodies may be mixed, or separate from each other, i.e., in different vessels.

[0081]Any of the above-described antibodies may bind to an epitope set forth in Table 1.

TABLE-US-00001 TABLE 1 Epitopes HPV Starting Sequence type AA (K/R)-(K/R)-R-F-H-(N/K/S/E/R)-I-(A/S) 59 124 F-H-(N/K/S/E/R)-I-(A/S)-(G/H)-X-(W/Y) 59 127 H-(N/K/S/E/R)-I-(A/S)-(G/H)-(R/Q)-(W/Y)-(T/K/R) 59 128 P-(E/A/Q)-E-K-(Q/L/K/R)-(R/K/L)-(H/V/I/L)-(V/L/C) 26 112 (G/H)-(R/Q/T/M/G/A/Y/H/S/N/I)-(W/Y/F)-(T/R/K/A)-G-(R/Q/S/L)-C-(R/L/M/A/T) 59 132 (W/Y/F)-(T/R/K/A)-G-(R/Q/S/L)-C-(R/L/M/A/T)-(L/R/A/T)-(N/R/S/A/Q/G) 59 134 G-(R/Q/S/L)-C-(R/L/M/A/T)-(L/R/A/T)-(N/R/S/A/Q/G)-C-(W/C/R) 59 136 (R/K)-P-(R/Y)-(K/T/S)-(L/V)-(H/P)-(D/E/H/Q)-L 59 10 (M/R/L)-F-(E/Q/D/H)-(D/N)-(P/T)-(Q/R/A/E/T)-(E/Q)-(R/K) 59 3 (D/N)-(P/T)-(Q/R/A/E/T)-(E/Q)-(R/K)-(R/K)-P-(R/Y) 59 6 (L/V)-(H/P)-(D/E/Q)-L-(C/S)-(E/T/Q)-(E/V/A/T)-(L/V)-(N/E/D) 59 14 (D/E/N)-(L/V/I)-(Q/E/R/T)-(L/V/I)-(Q/N/D/S/A/N)-C-V-(F/Y/E)- 59 26 L-(L/S)-I-R-C-(I/Y/H/L/M)-(R/I/C)-C 59 101 (R/I/C)-C-(Q/L)-(K/R)-P-L-(C/T/G/N)-P 59 107 (K/R)-P-L-(C/T/G/N)-P-(E/A/Q)-E-K 59 110 P-(E/A/Q)-E-K-(Q/L/K)-(R/L/K)-(H/I)-(L/V/C) 26 112 K-(Q/L/K)-(R/L/K)-(H/I)-(L/V/C)-(D/E/N)-(E/D/Y/L/K/S)-(K/N) 26 115 (L/V/C)-(D/E/N)-(E/D/Y/L/K/S)-(K/N)-(K/R)-R-F-H 26 119 I-(A/S)-(G/H)-(R/Q)-(W/Y)-(T/K/R)-G-(R/Q/L/S) 26 128 (W/Y)-(T/K/R)-G-(R/Q/L/S)-C-(M/A/L/R/T)-(N/S/A/R)-C 26 132

[0082]Certain hybridomas that produce the monoclonal antibodies described above and below may be deposited at the ATCC. Any of the deposited hybridomas, the antibodies produced by those hybridomas, as well as other antibodies that bind the same epitopes as the antibodies produced by those hybridomas, are also embodiments of this invention and may be claimed herein. Such antibodies may be employed in any of the methods described herein.

[0083]Methods for Detecting an HPV E6 Protein in a Sample

[0084]The invention provides a method of detecting an HPV E6 protein in a sample. In general, the methods involve contacting a subject antibody composition with a sample, and assessing any binding of the antibody to the sample. In most embodiments, binding of the antibody to the sample indicates the presence of an HPV E6 protein.

[0085]The antibodies of the invention may be screened for immunospecific binding by any method known in the art. The immunoassays which can be used include but are not limited to competitive and non-competitive assay systems using techniques such as western blots, radioimmunoassays, ELISA (enzyme linked immunosorbent assay), "sandwich" immunoassays, immunoprecipitation assays, precipitin reactions, gel diffusion precipitin reactions, immunodiffusion assays, agglutination assays, complement-fixation assays, immunoradiometric assays, fluorescent immunoassays, protein A immunoassays, and cellular immunostaining (fixed or native) assays to name but a few. Such assays are routine and well known in the art (see, e.g., Ausubel et al., eds, 1994, Current Protocols in Molecular Biology, Vol. 1, John Wiley & Sons, Inc., New York, which is incorporated by reference herein in its entirety). Exemplary immunoassays are described briefly below (but are not intended by way of limitation).

[0086]Immunoprecipitation protocols generally involve lysing a population of cells in a lysis buffer such as RIPA buffer (1% NP-40 or Triton X-100, 1% sodium deoxycholate, 0.1% SDS, 0.15 M NaCl, 0.01 M sodium phosphate at pH 7.2, 1% Trasylol) supplemented with protein phosphatase and/or protease inhibitors (e.g., EDTA, PMSF, aprotinin, sodium vanadate), adding the antibody of interest to the cell lysate, incubating for a period of time (e.g., 1-4 hours) at 4° C., adding protein A and/or protein G sepharose beads to the cell lysate, incubating for about an hour or more at 4° C., washing the beads in lysis buffer and resuspending the beads in SDS/sample buffer. The ability of the antibody of interest to immunoprecipitate a particular antigen can be assessed by, e.g., western blot analysis. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the binding of the antibody to an antigen and decrease the background (e.g., pre-clearing the cell lysate with sepharose beads).

[0087]Western blot analysis generally involves preparation of protein samples followed by electrophoresis of the protein samples in a polyacrylamide gel (e.g., 8%-20% SDS-PAGE depending on the molecular weight of the antigen), and transfer of the separated protein samples from the polyacrylamide gel to a membrane such as nitrocellulose, PVDF or nylon. Following transfer, the membrane is blocked in blocking solution (e.g., PBS with 3% BSA or non-fat milk), washed in washing buffer (e.g., PBS-Tween 20), and incubated with primary antibody (the antibody of interest) diluted in blocking buffer. After this incubation, the membrane is washed in washing buffer, incubated with a secondary antibody (which recognizes the primary antibody, e.g., an anti-human antibody) conjugated to an enzymatic substrate (e.g., horseradish peroxidase or alkaline phosphatase) or radioactive molecule (e.g., 32P or 125I), and after a further wash, the presence of the antigen may be detected. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the signal detected and to reduce the background noise.

[0088]ELISAs involve preparing antigen, coating the well of a 96 well multiwell plate with the antigen, adding the antibody of interest conjugated to a detectable compound such as an enzymatic substrate (e.g., horseradish peroxidase or alkaline phosphatase) to the well and incubating for a period of time, and detecting the presence of the antigen. In ELISAs the antibody of interest does not have to be conjugated to a detectable compound; instead, a second antibody (which recognizes the antibody of interest) conjugated to a detectable compound may be added to the well. Further, instead of coating the well with the antigen, the antibody may be coated to the well. In this case, a second antibody conjugated to a detectable compound may be added following the addition of the antigen of interest to the coated well. One of skill in the art would be knowledgeable as to the parameters that can be modified to increase the signal detected as well as other variations of ELISAs known in the art.

[0089]The binding affinity of an antibody to an antigen and the off-rate of an antibody-antigen interaction can be determined by competitive binding assays. One example of a competitive binding assay is a radioimmunoassay comprising the incubation of labeled antigen (e.g., ³H or ¹²⁵I) with the antibody of interest in the presence of increasing amounts of unlabeled antigen, and the detection of the antibody bound to the labeled antigen. The affinity of the antibody of interest for a particular antigen and the binding off-rates can be determined from the data by scatchard plot analysis. Competition with a second antibody can also be determined using radioimmunoassays. In this case, the antigen is incubated with antibody of interest conjugated to a labeled compound (e.g., ³H or ¹²⁵I) in the presence of increasing amounts of an unlabeled second antibody.

[0090]Antibodies of the invention may be screened using immunocytochemistry methods on cells (e.g., mammalian cells, such as CHO cells) transfected with a vector enabling the expression of an antigen or with vector alone using techniques commonly known in the art. Antibodies that bind antigen transfected cells, but not vector-only transfected cells, are antigen specific.

[0091]In certain embodiments, however, the assay is an antigen capture assay, and an array or microarray of antibodies may be employed for this purpose. Methods for making and using microarrays of polypeptides are known in the art (see e.g. U.S. Pat. Nos. 6,372,483, 6,352,842, 6,346,416 and 6,242,266).

[0092]Systems for Detecting an Oncogenic HPV E6 Protein

[0093]The invention provides a system for detecting the presence of an oncogenic HPV E6 polypeptide in a sample. In general, the system comprises a first and a second binding partner for an oncogenic HPV E6 polypeptide. In most embodiments, the first binding partner is a PDZ domain protein and the second binding partner is a subject antibody.

[0094]The subject antibodies may be used along with certain PDZ domain proteins as part of a system for detecting E6 protein from oncogenic strains of HPV. As mentioned above, oncogenic HPV E6 proteins contain a "PDZ-ligand" ("PL") that is bound by certain PDZ domain polypeptides. Non-oncogenic HPV E6 proteins do not contain such a PDZ-ligand, and, accordingly, are not bound by PDZ-domain polypeptides. Many PDZ domains suitable for use in the subject system are generally described in Table 2, and include MAGI-1 PDZ domain 2, the PDZ domain of TIP-1, and the PDZ domains 1 and 2 of DLG1, and many others. As would be recognized by one of skill in the art, a PDZ domain may be employed as part of a fusion protein, particularly in embodiments in which the PDZ domain polypeptide is anchored to a substrate. Accordingly, the subject system generally contains a suitable PDZ domain polypeptide, which is usually a fusion protein, and a subject antibody.

[0095]In certain embodiments, one of the binding partners is attached to a solid support, and the other binding partner may be labeled or part of a signal producing system. Proteins may be covalently bound or noncovalently attached through nonspecific bonding. If covalent bonding between the fusion protein and the surface is desired, the surface will usually be polyfunctional or be capable of being polyfunctionalized. Functional groups which may be present on the surface and used for linking can include carboxylic acids, aldehydes, amino groups, cyano groups, ethylenic groups, hydroxyl groups, mercapto groups and the like. The manner of linking a wide variety of compounds to various surfaces is well known and is amply illustrated in the literature.

TABLE-US-00002 TABLE 2 SEQ ID GI or NO. name Acc. # Sequence 106 AF6 domain 1 430993 LRKEPEIITVTLKKQNGMGLSIVAAKGAGQDKLGIYVKS VVKGGAADVDGRLAAGDQLLSVDGRSLVGLSQERAAEL MTRTSSVVTLEVAKQG 107 AIPC domain 1 12751451 LIRPSVISIIGLYKEKGKGLGFSIAGGRDCIRGQMGIFVKTI FPNGSAAEDGRLKEGDEILDVNGIPIKGLTFQEAIHTFKQI RSGLFVLTVRTKLVSPSLTNSS 108 AIPC domain 3 12751451 QSENEEDVCFIVLNRKEGSGLGFSVAGGTDVEPKSITVHR VFSQGAASQEGTMNRGDFLLSVNGASLAGLAHGNVLKV LHQAQLHKDALVVIKKGMDQPRPSNSS 109 AIPC domain 2 12751451 GISSLGRKTPGPKDRIVMEVTLNKEPRVGLGIGACCLALE NSPPGIYIHSLAPGSVAKMESNLSRGDQILEVNSVNVRHA ALSKVHAILSKCPPGPVRLVIGRHPNPKVSEQEMDEVIAR STYQESKEANSS 110 AIPC domain 4 12751451 LGRSVAVHDALCVEVLKTSAGLGLSLDGGKSSVTGDGP LVIKRVYKGGAAEQAGIIEAGDEILAINGKPLVGLMHFD AWNIMKSVPEGPVQLLIRKHRNSS 111 ALP domain 1 2773059 REEGGMPQTVILPGPAPWGFRLSGGIDFNQPLVITRITPGS KAAAANLCPGDVILAIDGFGTESMTHADAQDRIKAAAH QLCLKIDRGETHLWSPNSS 112 APXL1 domain 1 13651263 ILVEVQLSGGAPWGFTLKGGREHGEPLVITKIEEGSKAAA VDKLLAGDEIVGINDIGLSGFRQEAICLVKGSHKTLKLVV KRNSS 113 CARD11 domain 1 12382772 SVGHVRGPGPSVQHTTLNGDSLTSQLTLLGGNARGSFVH SVKPGSLAEKAGLREGHQLLLLEGCIRGERQSVPLDTCT KEEAHWTIQRCSGPVTLHYKVTNHEGYRK 114 CARD14 domain 1 13129123 RRPARRILSQVTMLAFQGDALLEQISVIGGNLTGIFIHRVT PGSAADQMALRPGTQIVMVDYEASEPLFKAVLEDTTLEE AVGLLRRVDGFCCLSVKVNTDGYKR 115 CARD14 domain 1 13129123 ILSQVTMLAFQGDALLEQISVIGGNLTGIFIHRVTPGSAAD QMALRPGTQIVMVDYEASEPLFKAVLEDTTLEEAVGLLR RVDGFCCLSVKVNTDGYKRL 116 CASK domain 1 3087815 TRVRLVQFQKNTDEPMGITLKMNELNHCIVARIMHGGMI HRQGTLHVGDEIREINGISVANQTVEQLQKMLREMRGSI TFKIVPSYRTQS 117 CNK1 domain 1 3930780 LEQKAVLEQVQLDSPLGLEIHTTSNCQHFVSQVDTQVPT DSRLQIQPGDEVVQINEQVVVGWPRKNMVRELLREPAG LSLVLKKIPIP 118 Cytohesin binding 3192908 QRKLVTVEKQDNETFGFEIQSYRPQNQNACSSEMFTLICK Protein domain 1 IQEDSPAHCAGLQAGDVLANINGVSTEGFTYKQVVDLIR SSGNLLTIETLNG 119 Densin domain 1 16755892 RCLIQTKGQRSMDGYPEQFCVRIEKNPGLGFSISGGISGQ GNPFKPSDKGIFVTRVQPDGPASNLLQPGDKILQANGHSF VHMEHEKAVLLLKSFQNTVDLVIQRELTV 120 DLG 6 splice AB053303 PTSPEIQELRQMLQAPHFKGATIKRHEMTGDILVARIIHG variant 2 domain 1 GLAERSGLLYAGDKLVEVNGVSVEGLDPEQVIHILAMSR GTIMFKVVPVSDPPVNSS 121 DLG 6 splice 14647140 PTSPEIQELRQMLQAPHFKALLSAHDTIAQKDFEPLLPPLP variant 1 domain 1 DNIPESEEAMRIVCLVKNQQPLGATIKRHEMTGDILVARII HGGLAERSGLLYAGDKLVEVNGVSVEGLDPEQVIHILAM SRGTIMFKVVPVSDPPVNSS 122 DLG1 domain 1 475816 IQVNGTDADYEYEEITLERGNSGLGFSIAGGTDNPHIGDD SSIFITKIITGGAAAQDGRLRVNDCILQVNEVDVRDVTHS KAVEALKEAGSIVRLYVKRRN 123 DLG1 domain 2 475816 IQLIKGPKGLGFSIAGGVGNQHIPGDNSIYVTKIIEGGAAH KDGKLQIGDKLLAVNNVCLEEVTHEEAVTALKNTSDFV YLKVAKPTSMYMNDGN 124 DLG1 domains 1 475816 VNGTDADYEYEEITLERGNSGLGFSIAGGTDNPHIGDDSS and 2 IFITKIITGGAAAQDGRLRVNDCILQVNEVDVRDVTHSKA VEALKEAGSIVRLYVKRRKPVSEKIMEIKLIKGPKGLGFSI AGGVGNQHIPGDNSIYVTKIIEGGAAHKDGKLQIGDKLL AVNNVCLEEVTHEEAVTALKNTSDFVYLKVAKPTSMYM NDGYA 125 DLG1 domain 3 475816 ILHRGSTGLGFNIVGGEDGEGIFISFILAGGPADLSGELRK GDRIISVNSVDLRAASHEQAAAALKNAGQAVTIVAQYRP EEYSR 126 DLG2 domain 3 12736552 IEGRGILEGEPRKVVLHKGSTGLGFNIVGGEDGEGIFVSFI LAGGPADLSGELQRGDQILSVNGIDLRGASHEQAAAALK GAGQTVTIIAQHQPEDYARFEAKIHDLNSS 127 DLG2 domain 1 12736552 ISYVNGTEIEYEFEEITLERGNSGLGFSIAGGTDNPHIGDD PGIFITKIIPGGAAAEDGRLRVNDCILRVNEVDVSEVSHSK AVEALKEAGSIVRLYVRRR 128 DLG2 domain 2 12736552 IPILETVVEIKLFKGPKGLGFSIAGGVGNQHIPGDNSIYVT KIIDGGAAQKDGRLQVGDRLLMVNNYSLEEVTHEEAVAI LKNTSEVVYLKVGKPTTIYMTDPYGPPNSSLTD 129 DLG5 domain 1 3650451 GIPYVEEPRHVKVQKGSEPLGISIVSGEKGGIYVSKVTVG SIAHQAGLEYGDQLLEFNGINLRSATEQQARLIIGQQCDTI TILAQYNPHVHQLRNSSLTD 130 DLG5 domain 2 3650451 GILAGDANKKTLEPRVVFIKKSQLELGVHLCGGNLHGVF VAEVEDDSPAKGPDGLVPGDLILEYGSLDVRNKTVEEVY VEMLKPRDGVRLKVQYRPEEFIVTD 131 DVL1 domain 1 2291005 LNIVTVTLNMERHHFLGISIVGQSNDRGDGGIYIGSIMKG GAVAADGRIEPGDMLLQVNDVNFENMSNDDAVRVLREI VSQTGPISLTVAKCW 132 DVL2 domain 1 2291007 LNIITVTLNMEKYNFLGISIVGQSNERGDGGIYIGSIMKGG AVAADGRIEPGDMLLQVNDMNFENMSNDDAVRVLRDI VHKPGPIVLTVAKCWDPSPQNS 133 DVL3 domain 1 6806886 IITVTLNMEKYNFLGISIVGQSNERGDGGIYIGSIMKGGAV AADGRIEPGDMLLQVNEINFENMSNDDAVRVLREIVHKP GPITLTVAKCWDPSP 134 EBP50 domain 2 3220018 QQRELRPRLCTMKKGPSGYGFNLHSDKSKPGQFIRSVDP DSPAEASGLRAQDRIVEVNGVCMEGKQHGDVVSAIRAG GDETKLLVVDRETDEFFKNSS 135 EBP50 domain 1 3220018 GIQMSADAAAGAPLPRLCCLEKGPNGYGFHLHGEKGKL GQYIRLVEPGSPAEKAGLLAGDRLVEVNGENVEKETHQ QVVSRIRAALNAVRLLVVDPETDEQLQKLGVQVREELLR AQEAPGQAEPPAAAEVQGAGNENEPREADKSHPEQREL RN 136 EBP50 domains 1 3220018 GIQMSADAAAGAPLPRLCCLEKGPNGYGFHLHGEKGKL and 2 GQYIRLVEPGSPAEKAGLLAGDRLVEVNGENVEKETHQ QVVSRIRAALNAVRLLVVDPETDEQLQKLGVQVREELLR AQEAPGQAEPPAAAEVQGAGNENEPREADKSHPEQREL RPRLCTMKKGPSGYGFNLHSDKSKPGQFIRSVDPDSPAE ASGLRAQDRIVEVNGVCMEGKQHGDVVSAIRAGGDETK LLVVDRETDEFFK 137 EBP50 domain 1 3220018 QMSADAAAGAPLPRLCCLEKGPNGYGFHLHGEKGKLGQ YIRLVEPGSPAEKAGLLAGDRLVEVNGENVEKETHQQV VSRIRAALNAVRLLVVDPETDEQLQKLGVQVREELLRAQ EAPGQAEPPAAAEVQGAGNENEPREADKSHPEQRELRNSS 138 ELFIN 1 domain 1 2957144 LTTQQIDLQGPGPWGFRLVGGKDFEQPLAISRVTPGSKA ALANLCIGDVITAIDGENTSNMTHLEAQNRIKGCTDNLTL TVARSEHKVWSPLVTNSSW 139 ENIGMA domain 1 561636 IFMDSFKVVLEGPAPWGFRIQGGKDFNVPLSISRLTPGGK AAQAGVAVGDWVLSIDGENAGSLTHIEAQNKIRACGER LSLGLSRAQPV 140 ERBIN domain 1 8923908 QGHELAKQEIRVRVEKDPELGFSISGGVGGRGNPFRPDD DGIFVTRVQPEGPASKLLQPGDKIIQANGYSFINIEHGQAV SLLKTFQNTVELIIVREVSS 141 FLJ00011 domain 1 10440352 KNPSGELKTVTLSKMKQSLGISISGGIESKVQPMVKIEKIF PGGAAFLSGALQAGFELVAVDGENLEQVTHQRAVDTIR RAYRNKAREPMELVVRVPGPSPRPSPSD 142 FLJ11215 domain 1 11436365 EGHSHPRVVELPKTEEGLGFNIMGGKEQNSPIYISRIIPGGI ADRHGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAAQ GKVKLVVRYTPKVLEEME 143 FLJ12428 domain 1 BC012040 PGAPYARKTFTIVGDAVGWGFVVRGSKPCHIQAVDPSGP AAAAGMKVCQFVVSVNGLNVLHVDYRTVSNLILTGPRT IVMEVMEELEC 144 FLJ12615 domain 1 10434209 GQYGGETVKIVRIEKARDIPLGATVRNEMDSVIISRIVKG GAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMH GTLTFVLIPSQQIKPPPA 145 FLJ21687 domain 1 10437836 KPSQASGHFSVELVRGYAGFGLTLGGGRDVAGDTPLAV RGLLKDGPAQRCGRLEVGDLVLHINGESTQGLTHAQAV ERIRAGGPQLHLVIRRPLETHPGKPRGV 146 FLJ31349 domain 1 AK055911 PVMSQCACLEEVHLPNIKPGEGLGMYIKSTYDGLHVITG TTENSPADRSQKIHAGDEVTQVNQQTVVGWQLKNLVKK LRENPTGVVLLLKKRPTGSFNFTP 147 FLJ32798 domain 1 AK057360 IDDEEDSVKIIRLVKNREPLGATIKKDEQTGAIIVARIMRG GAADRSGLIHVGDELREVNGIPVEDKRPEEIIQILAQSQG AITFKIIPGSKEETPS 148 GORASP 2 13994253 MGSSQSVEIPGGGTEGYHVLRVQENSPGHRAGLEPFFDFI domains 1 and 2 VSINGSRLNKDNDTLKDLLKANVEKPVKMLIYSSKTLEL RETSVTPSNLWGGQGLLGVSIRFCSFDGANENVWHVLEV ESNSPAALAGLRPHSDYIIGADTVMNESEDLFSLIETHEA KPLKLYVYNTDTDNCREVIITPNSAWGGEGSLGCGIGYG YLHRIPTRPFEEGKKISLPGQMAGTPITPLKDGFTEVQLSS VNPPSLSPPGTTGIEQSLTGLSISSTPPAVSSVLSTGVPTVP LLPPQVNQSLTSVPPMNPATTLPGLMPLPAGLPNLPNLNL NLPAPHIMPGVGLPELVNPGLPPLPSMPPRNLPGIAPLPLP SEFLPSFPLVPESSSAASSGELLSSLPPTSNAPSDPATTTAK ADAASSLTVDVTPPTAKAPTTVEDRVGDSTPVSEKPVSA AVDANASESP 149 GORASP 2 domain 2 13994253 NENVWHVLEVESNSPAALAGLRPHSDYIIGADTVMNESE DLFSLIETHEAKPLKLYVYNTDTDNCREVIITPNSAWGGE GSLGCGIGYGYLHRIPTR 150 GORASP 2 domain 1 13994253 MGSSQSVEIPGGGTEGYHVLRVQENSPGHRAGLEPFFDFI VSINGSRLNKDNDTLKDLLKANVEKPVKMLIYSSKTLEL RETSVTPSNLWGGQGLLGVSIRFCSFDGANE 151 GORASP 1 domain 2 29826292 RASEQVWHVLDVEPSSPAALAGLRPYTDYVVGSDQILQE SEDFFTLIESHEGKPLKLMVYNSKSDSCREVTVTPNAAW GGEGSLGCGIGYGYLHRIPTQ 152 GORASP 1 domain 1 29826292 MGLGVSAEQPAGGAEGFHLHGVQENSPAQQAGLEPYFD FIITIGHSRLNKENDTLKALLKANVEKPVKLEVFNMKTM RVREVEVVPSNMWGGQGLLGASVRFCSFRRASE 153 GORASP 1 29826292 MGLGVSAEQPAGGAEGFHLHGVQENSPAQQAGLEPYFD domains 1 and 2 FIITIGHSRLNKENDTLKALLKANVEKPVKLEVFNMKTM RVREVEVVPSNMWGGQGLLGASVRFCSFRRASEQVWH VLDVEPSSPAALAGLRPYTDYVVGSDQILQESEDFFTLIES HEGKPLKLMVYNSKSDSCREVTVTPNAAWGGEGSLGCG IGYGYLHRIPTQPPSYHKKPPGTPPPSALPLGAPPPDALPP GPTPEDSPSLETGSRQSDYMEALLQAPGSSMEDPLPGPGS PSHSAPDPDGLPHFMETPLQPPPPVQRVMDPGFLDVSGIS LLDNSNASVWPSLPSSTELTTTAVSTSGPEDICSSSSSHER GGEATWSGSEFEVSFLDSPGAQAQADHLPQLTLPDSLTS AASPEDGLSAELLEAQAEEEPASTEGLDTGTEAEGLDSQ AQISTTE 154 GRIP 1 domain 6 4539083 IYTVELKRYGGPLGITISGTEEPFDPIIISSLTKGGLAERTG AIHIGDRILAINSSSLKGKPLSEAIHLLQMAGETVTLKIKK QTDAQSA 155 GRIP 1 domain 1 4539083 VVELMKKEGTTLGLTVSGGIDKDGKPRVSNLRQGGIAAR SDQLDVGDYIKAVNGINLAKFRHDEIISLLKNVGERVVLE VEYE 156 GRIP 1 domain 3 4539083 HVATASGPLLVEVAKTPGASLGVALTTSMCCNKQVIVID KIKSASIADRCGALHVGDHILSIDGTSMEYCTLAEATQFL ANTTDQVKLEILPHHQTRLALKGPNSS 157 GRIP 1 domain 7 4539083 IMSPTPVELHKVTLYKDSDMEDFGFSVADGLLEKGVYV KNIRPAGPGDLGGLKPYDRLLQVNHVRTRDFDCCLVVPL IAESGNKLDLVISRNPLA 158 GRIP 1 domain 4 4539083 IYTVELKRYGGPLGITISGTEEPFDPIIISSLTKGGLAERTG AIHIGDRILAINSSSLKGKPLSEAIHLLQMAGETVTLKIKK QTDAQSA 159 GRIP 1 domain 5 4539083 IMSPTPVELHKVTLYKDSDMEDFGFSVADGLLEKGVYV KNIRPAGPGDLGGLKPYDRLLQVNHVRTRDFDCCLVVPL

IAESGNKLDLVISRNPLA 160 GTPase activating 2389008 SRGCETRELALPRDGQGRLGFEVDAEGFVTHVERFTFAE enzyme domain 1 TAGLRPGARLLRVCGQTLPSLRPEAAAQLLRSAPKVCVT VLPPDESGRP 161 Guanine exchange 6650765 CSVMIFEVVEQAGAIILEDGQELDSWYVILNGTVEISHPD factor domain 1 GKVENLFMGNSFGITPTLDKQYMHGIVRTKVDDCQFVCI AQQDYWRILNHVEKNTHKVEEEGEIVMVH 162 HEMBA 1000505 10436367 PRETVKIPDSADGLGFQIRGFGPSVVHAVGRGTVAAAAG domain 2 LHPGQCIIKVNGINVSKETHASVIAHVTACRKYRRPTKQD SIQ 163 HEMBA 1000505 10436367 LENVIAKSLLIKSNEGSYGFGLEDKNKVPIIKLVEKGSNA domain 1 EMAGMEVGKKIFAINGDLVFMRPFNEVDCFLKSCLNSRK PLRVLVSTKP 164 HEMBA 1003117 7022001 EDFCYVFTVELERGPSGLGMGLIDGMHTHLGAPGLYIQT domain 1 LLPGSPAAADGRLSLGDRILEVNGSSLLGLGYLRAVDLIR HGGKKMRFLVAKSDVETAKKI 165 hShroom domain 1 18652858 IYLEAFLEGGAPWGFTLKGGLEHGEPLIISKVEEGGKADT LSSKLQAGDEVVHINEVTLSSSRKEAVSLVKGSYKTLRL VVRRDVCTDPGH 166 HSPC227 domain 1 7106843 NNELTQFLPRTITLKKPPGAQLGFNIRGGKASQLGIFISKV IPDSDAHRAGLQEGDQVLAVNDVDFQDIEHSKAVEILKT AREISMRVRFFPYNYHRQKE 167 HTRA 3 domain 1 AY040094 FLTEFQDKQIKDWKKRFIGIRMRTITPSLVDELKASNPDFP EVSSGIYVQEVAPNSPSQRGGIQDGDIIVKVNGRPLVDSS ELQEAVLTESPLLLEVRRGNDDLLFS 168 HTRA 4 domain 1 AL576444 NKKYLGLQMLSLTVPLSEELKMHYPDFPDVSSGVYVCK VVEGTAAQSSGLRDHDVIVNINGKPITTTTDVVKALDSD SLSMAVLRGKDNLLLTV 169 INADL domain 3 2370148 PGSDSSLFETYNVFLVRKDGQSLGIRIVGYVGTSHTGEAS GIYVKSIIPGSAAYHNGHIQVNDKIVAVDGVNIQGFANHD VVEVLRNAGQVVHLTLVRRKTSSSTSRIHRD 170 INADL domain 8 2370148 PATCPIVPGQEMIIEISKGRSGLGLSIVGGKDTPLNAIVIHE VYEEGAAARDGRLWAGDQILEVNGVDLRNSSHEEAITA LRQTPQKVRLVVY 171 INADL domain 2 2370148 LPETVCWGHVEEVELINDGSGLGFGIVGGKTSGVVVRTI VPGGLADRDGRLQTGDHILKIGGTNVQGMTSEQVAQVL RNCGNSVRMLVARDPAGDIQSPI 172 INADL domain 6 2370148 PNFSHWGPPRIVEIFREPNVSLGISIVVGQTVIKRLKNGEE LKGIFIKQVLEDSPAGKTNALKTGDKILEVSGVDLQNASH SEAVEAIKNAGNPVVFIVQSLSSTPRVIPNVHNKANSS 173 INADL domain 7 2370148 PGELHIIELEKDKNGLGLSLAGNKDRSRMSIFVVGINPEG PAAADGRMRIGDELLEINNQILYGRSHQNASAIIKTAPSK VKLVFIRNEDAVNQMANSS 174 INADL domain 5 2370148 LSSPEVKIVELVKDCKGLGFSILDYQDPLDPTRSVIVIRSL VADGVAERSGGLLPGDRLVSVNEYCLDNTSLAEAVEILK AVPPGLVHLGICKPLVEFIVTD 175 INADL domain 1 2370148 IWQIEYIDIERPSTGGLGFSVVALRSQNLGKVDIFVKDVQ PGSVADRDQRLKENDQILAINHTPLDQNISHQQAIALLQQ TTGSLRLIVAREPVHTKSSTSSSE 176 INADL domain 4 2370148 NSDDAELQKYSKLLPIHTLRLGVEVDSFDGHHYISSVSG GPVDTLGLLQPEDELLEVNGMQLYGKSRREAVSFLKEVP PPFTLVCCRRLFDDEAS 177 KIAA0313 domain 1 7657260 HLRLLNIACAAKAKRRLMTLTKPSREAPLPFILLGGSEKG FGIFVDSVDSGSKATEAGLKRGDQILEVNGQNFENIQLSK AMEILRNNTHLSITVKTNLFVFKELLTRLSEEKRNGAP 178 KIAA0316 domain 1 6683123 IPPAPRKVEMRRDPVLGFGFVAGSEKPVVVRSVTPGGPSE GKLIPGDQIVMINDEPVSAAPRERVIDLVRSCKESILLTVI QPYPSPK 179 KIAA0340 domain 1 2224620 LNKRTTMPKDSGALLGLKVVGGKMTDLGRLGAFITKVK KGSLADVVGHLRAGDEVLEWNGKPLPGATNEEVYNIILE SKSEPQVEIIVSRPIGDIPRIHRD 180 KIAA0380 domain 1 2224700 RCVIIQKDQHGFGFTVSGDRIVLVQSVRPGGAAMKAGVK EGDRIIKVNGTMVTNSSHLEVVKLIKSGAYVALTLLGS 181 KIAA0382 domain 1 7662087 ILVQRCVIIQKDDNGFGLTVSGDNPVFVQSVKEDGAAMR AGVQTGDRIIKVNGTLVTHSNHLEVVKLIKSGSYVALTV QGRPPGNSS 182 KIAA0440 domain 1 2662160 SVEMTLRRNGLGQLGFHVNYEGIVADVEPYGYAWQAG LRQGSRLVEICKVAVATLSHEQMIDLLRTSVTVKVVIIPPH 183 KIAA0545 domain 1 14762850 LKVMTSGWETVDMTLRRNGLGQLGFHVKYDGTVAEVE DYGFAWQAGLRQGSRLVEICKVAVVTLTHDQMIDLLRT SVTVKVVIIPPFEDGTPRRGW 184 KIAA0559 domain 1 3043641 HYIFPHARIKITRDSKDHTVSGNGLGIRIVGGKEIPGHSGEI GAYIAKILPGGSAEQTGKLMEGMQVLEWNGIPLTSKTYE EVQSIISQQSGEAEICVRLDLNML 185 KIAA0613 domain 1 3327039 SYSVTLTGPGPWGFRLQGGKDFNMPLTISRITPGSKAAQS QLSQGDLVVAIDGVNTDTMTHLEAQNKIKSASYNLSLTL QKSKNSS 186 KIAA0858 domain 1 4240204 FSDMRISINQTPGKSLDFGFTIKWDIPGIFVASVEAGSPAE FSQLQVDDEIIAINNTKFSYNDSKEWEEAMAKAQETGHL VMDVRRYGKAGSPE 187 KIAA0902 domain 1 4240292 QSAHLEVIQLANIKPSEGLGMYIKSTYDGLHVITGTTENS PADRCKKIHAGDEVIQVNHQTVVGWQLKNLVNALREDP SGVILTLKKRPQSMLTSAPA 188 KIAA0967 domain 1 4589577 ILTQTLIPVRHTVKIDKDTLLQDYGFHISESLPLTVVAVTA GGSAHGKLFPGDQILQMNNEPAEDLSWERAVDILREAED SLSITVVRCTSGVPKSSNSS 189 KIAA1202 domain 1 6330421 RSFQYVPVQLQGGAPWGFTLKGGLEHCEPLTVSKIEDGG KAALSQKMRTGDELVNINGTPLYGSRQEALILIKGSFRIL KLIVRRRNAPVS 190 KIAA1222 domain 1 6330610 ILEKLELFPVELEKDEDGLGISIIGMGVGADAGLEKLGIFV KTVTEGGAAQRDGRIQVNDQIVEVDGISLVGVTQNFAAT VLRNTKGNVRFVIGREKPGQVSE 191 KIAA1284 domain 1 6331369 KDVNVYVNPKKLTVIKAKEQLKLLEVLVGIIHQTKWSW RRTGKQGDGERLVVHGLLPGGSAMKSGQVLIGDVLVAV NDVDVTTENIERVLSCIPGPMQVKLTFENAYDVKRET 192 KIAA1389 domain 1 7243158 TRGCETVEMTLRRNGLGQLGFHVNFEGIVADVEPFGFA WKAGLRQGSRLVEICKVAVATLTHEQMIDLLRTSVTVK VVIIQPHDDGSPRR 193 KIAA1415 domain 1 7243210 VENILAKRLLILPQEEDYGFDIEEKNKAVVVKSVQRGSLA EVAGLQVGRKIYSINEDLVFLRPFSEVESILNQSFCSRRPL RLLVATKAKEIIKIP 194 KIAA1526 domain 1 5817166 PDSAGPGEVRLVSLRRAKAHEGLGFSIRGGSEHGVGIYVS LVEPGSLAEKEGLRVGDQILRVNDKSLARVTHAEAVKAL KGSKKLVLSVYSAGRIPGGYVTNH 195 KIAA1526 domain 2 5817166 LQGGDEKKVNLVLGDGRSLGLTIRGGAEYGLGIYITGVD PGSEAEGSGLKVGDQILEVNGRSFLNILHDEAVRLLKSSR HLILTVKDVGRLPHARTTVDE 196 KIAA1620 domain 1 10047316 LRRAELVEIIVETEAQTGVSGINVAGGGKEGIFVRELRED SPAARSLSLQEGDQLLSARVFFENFKYEDALRLLQCAEP YKVSFCLKRTVPTGDLALR 197 KIAA1719 domain 5 1267982 IQTTGAVSYTVELKRYGGPLGITISGTEEPFDPIVISGLTKR GLAERTGAIHVGDRILAINNVSLKGRPLSEAIHLLQVAGE TVTLKIKKQLDR 198 KIAA1719 domain 6 1267982 ILEMEELLLPTPLEMHKVTLHKDPMRHDFGFSVSDGLLE KGVYVHTVRPDGPAHRGGLQPFDRVLQVNHVRTRDFDC CLAVPLLAEAGDVLELIISRKPHTAHSS 199 KIAA1719 domain 2 1267982 IHTVANASGPLMVEIVKTPGSALGISLTTTSLRNKSVITID RIKPASVVDRSGALHPGDHILSIDGTSMEHCSLLEATKLL ASISEKVRLEILPVPQSQRPL 200 KIAA1719 domain 1 1267982 ITVVELIKKEGSTLGLTISGGTDKDGKPRVSNLRPGGLAA RSDLLNIGDYIRSVNGIHLTRLRHDEIITLLKNVGERVVLE VEY 201 KIAA1719 domain 3 1267982 IQIVHTETTEVVLCGDPLSGFGLQLQGGIFATETLSSPPLV CFIEPDSPAERCGLLQVGDRVLSINGIATEDGTMEEANQL LRDAALAHKVVLEVEFDVAESV 202 KIAA1719 domain 1 1267982 ILDVSLYKEGNSFGFVLRGGAHEDGHKSRPLVLTYVRPG GPADREGSLKVGDRLLSVDGIPLHGASHATALATLRQCS HEALFQVEYDVATP 203 KIAA1719 domain 4 1267982 QFDVAESVIPSSGTFHVKLPKKRSVELGITISSASRKRGEP LIISDIKKGSVAHRTGTLEPGDKLLAIDNIRLDNCPMEDA VQILRQCEDLVKLKIRKDEDN 204 LIM mystique 12734250 MALTVDVAGPAPWGFRITGGRDFHTPIMVTKVAERGKA domain 1 KDADLRPGDIIVAINGESAEGMLHAEAQSKIRQSPSPLRL QLDRSQATSPGQT 205 LIM protein domain 1 3108092 SNYSVSLVGPAPWGFRLQGGKDFNMPLTISSLKDGGKAA QANVRIGDVVLSIDGINAQGMTHLEAQNKIKGCTGSLNM TLQRAS 206 LIMK1 domain 1 4587498 TLVEHSKLYCGHCYYQTVVTPVIEQILPDSPGSHLPHTVT LVSIPASSHGKRGLSVSIDPPHGPPGCGTEHSHTVRVQGV DPGCMSPDVKNSIHVGDRILEINGTPIRNVPLDEIDLLIQE TSRLLQLTLEHD 207 LIMK2 domain 1 1805593 PYSVTLISMPATTEGRRGFSVSVESACSNYATTVQVKEV NRMHISPNNRNAIHPGDRILEINGTPVRTLRVEEVEDAISQ TSQTLQLLIEHD 208 LIM-RIL domain 1 1085021 IHSVTLRGPSPWGFRLVGRDFSAPLTISRVHAGSKASLAA LCPGDLIQAINGESTELMTHLEAQNRIKGCHDHLTLSVSR PE 209 LU-1 domain 1 U52111 VCYRTDDEEDLGIYVGEVNPNSIAAKDGRIREGDRIIQIN GVDVQNREEAVAILSQEENTNISLLVARPESQLA 210 MAGI 1 domain 2 3370997 IPATQPELITVHIVKGPMGFGFTIADSPGGGGQRVKQIVDS PRCRGLKEGDLIVEVNKKNVQALTHNQVVDMLVECPKG SEVTLLVQRGGNSS 211 MAGI 1 domain 5 3370997 IPDYQEQDIFLWRKETGFGFRILGGNEPGEPIYIGHIVPLG AADTDGRLRSGDELICVDGTPVIGKSHQLVVQLMQQAA KQGHVNLTVRRKVVFAVPKTENSS 212 MAGI 1 domain 4 3370997 IPGVVSTVVQPYDVEIRRGENEGFGFVIVSSVSRPEAGTTF AGNACVAMPHKIGRIIEGSPADRCGKLKVGDRILAVNGC SITNKSHSDIVNLIKEAGNTVTLRIIPGDESSNAEFIVTD 213 MAGI 1 domain 1 3370997 IPSELKGKFIHTKLRKSSRGFGFTVVGGDEPDEFLQIKSLV LDGPAALDGKMETGDVIVSVNDTCVLGHTHAQVVKIFQ SIPIGASVDLELCRGYPLPFDPDGIHRD 214 MAGI 1 domain 3 3370997 QATQEQDFYTVELERGAKGFGFSLRGGREYNMDLYVLR LAEDGPAERCGKMRIGDEILEINGETTKNMKHSRAIELIK NGGRRVRLFLKRG 215 Magi 2 domain 1 2947231 REKPLFTRDASQLKGTFLSTTLKKSNMGFGFTIIGGDEPD EFLQVKSVIPDGPAAQDGKMETGDVIVYINEVCVLGHTH ADVVKLFQSVPIGQSVNLVLCRGYP 216 Magi 2 domain 3 2947231 HYKELDVHLRRMESGFGFRILGGDEPGQPILIGAVIAMGS ADRDGRLHPGDELVYVDGIPVAGKTHRYVIDLMHHAAR NGQVNLTVRRKVLCG 217 Magi 2 domain 4 2947231 EGRGISSHSLQTSDAVIHRKENEGFGFVIISSLNRPESGSTI TVPHKIGRIIDGSPADRCAKLKVGDRILAVNGQSIINMPH ADIVKLIKDAGLSVTLRIIPQEEL 218 Magi 2 domain 2 2947231 LSGATQAELMTLTIVKGAQGFGFTIADSPTGQRVKQILDI QGCPGLCEGDLIVEINQQNVQNLSHTEVVDILKDCPIGSE TSLIIHRGGFF 219 Magi 2 domain 5 2947231 LSDYRQPQDFDYFTVDMEKGAKGFGFSIRGGREYKMDL YVLRLAEDGPAIRNGRMRVGDQIIEINGESTRDMTHARAI ELIKSGGRRVRLLLKRGTGQ 220 Magi 2 domain 6 2947231 HESVIGRNPEGQLGFELKGGAENGQFPYLGEVKPGKVAY ESGSKLVSEELLLEVNETPVAGLTIRDVLAVIKHCKDPLR LKCVKQGGIHR 221 MAGI 3 domain 2 10047344 ASSGSSQPELVTIPLIKGPKGFGFAIADSPTGQKVKMILDS QWCQGLQKGDIIKEIYHQNVQNLTHLQVVEVLKQFPVG ADVPLLILRGGPPSPTKTAKM 222 MAGI 3 domain 5 10047344 QNLGCYPVELERGPRGFGFSLRGGKEYNMGLFILRLAED GPAIKDGRIHVGDQIVEINGEPTQGITHTRAIELIQAGGNK VLLLLRPGTGLIPDHGLA

223 MAGI 3 domain 3 10047344 LYEDKPPNTKDLDVFLRKQESGFGFRVLGGDGPDQSIYIG AIIPLGAAEKDGRLRAADELMCIDGIPVKGKSHKQVLDL MTTAARNGHVLLTVRRKIFYGEKQPEDDS 224 MAGI 3 domain 1 10047344 PSQLKGVLVRASLKKSTMGFGFTIIGGDRPDEFLQVKNV LKDGPAAQDGKIAPGDVIVDINGNCVLGHTHADVVQMF QLVPVNQYVNLTLCRGYPLPDDSED 225 MAGI 3 domain 4 10047344 PAPQEPYDVVLQRKENEGFGFVILTSKNKPPPGVIPHKIG RVIEGSPADRCGKLKVGDHISAVNGQSIVELSHDNIVQLI KDAGVTVTLTVIAEEEHHGPPS 226 MAST1 domain 1 4589589 GLRSPITIQRSGKKYGFTLRAIRVYMGDTDVYSVHHIVW HVEEGGPAQEAGLCAGDLITHVNGEPVHGMVHPEVVELI LKSGNKVAVTTTPFEN 227 MAST2 domain 1 3882334 ISALGSMRPPIIIHRAGKKYGFTLRAIRVYMGDSDVYTVH HMVWHVEDGGPASEAGLRQGDLITHVNGEPVHGLVHTE VVELILKSGNKVAISTTPLENSS 228 MAST3 domain 1 3043645 LCGSLRPPIVIHSSGKKYGFSLRAIRVYMGDSDVYTVHHV VWSVEDGSPAQEAGLRAGDLITHINGESVLGLVHMDVV ELLLKSGNKISLRTTALENTSIKVG 229 MAST4 domain 1 2224546 PHQPIVIHSSGKNYGFTIRAIRVYVGDSDIYTVHHIVWNV EEGSPACQAGLKAGDLITHINGEPVHGLVHTEVIELLLKS GNKVSITTTPF 230 MGC5395 domain 1 BC012477 PAKMEKEETRELLLPNWQGSGSHGLTIAQRDDGVFVQE VTQNSPAARTGVVKEGDQIVGATIYFDNLQSGEVTQLLN TMGHHTVGLKLHRKGDRSPNSS 231 MINT1 domain 1 2625024 SENCKdVFIEKQKGEILGVVIVESGWGSILPTVIIANMMH GGPAEKSGKLNIGDQIMSINGTSLVGLPLSTCQSIIKGLKN QSRVKLNIVRCPPVNSS 232 MINT1 domains 1 2625024 SENCKDVFIEKQKGEILGVVIVESGWGSILPTVIIANMMH and 2 GGPAEKSGKLNIGDQIMSINGTSLVGLPLSTCQSIIKGLEN QSRVKLNIVRCPPVTTVLIRRPDLRYQLGFSVQNGIICSLM RGGIAERGGVRVGHRIIEINGQSVVATPHEKIVHILSNAV GEIHMKTMPAAMYRLL 233 MINT1 domain 2 2625024 LRCPPVTTVLIRRPDLRYQLGFSVQNGIICSLMRGGIAERG GVRVGHRIIEINGQSVVATPHEKIVHILSNAVGEIHMKTM PAAMYRLLNSS 234 MINT3 domain 1 3169808 HNGDLDHFSNSDNCREVHLEKRRGEGLGVALVESGWGS LLPTAVIANLLHGGPAERSGALSIGDRLTAINGTSLVGLPL AACQAAVRETKSQTSVTLSIVHCPPVT 235 MINT3 domain 2 3169808 PVTTAIIHRPHAREQLGFCVEDGIICSLLRGGIAERGGIRV GHRIIEINGQSVVATPHARIIELLTEAYGEVHIKTMPAATY RLLTGNSS 236 MINT3 domain 1 3169808 LSNSDNCREVHLEKRRGEGLGVALVESGWGSLLPTAVIA NLLHGGPAERSGALSIGDRLTAINGTSLVGLPLAACQAA VRETKSQTSVTLSIVHCPPVTTAIM 237 MPP1 domain 1 189785 RKVRLIQFEKVTEEPMGITLKLNEKQSCTVARILHGGMIH RQGSLHVGDEILEINGTNVTNHSVDQLQKAMKETKGMIS LKVIPNQ 238 MPP2 domain 1 939884 PVPPDAVRMVGIRKTAGEHLGVTFRVEGGELVIARILHG GMVAQQGLLHVGDIIKEVNGQPVGSDPRALQELLRNAS GSVILKILPNYQ 239 MPP3 domain 1 21536463 NIDEDFDEESVKIVRLVKNKEPLGATIRRDEHSGAVVVA RIMRGGAADRSGLVHVGDELREVNGIAVLHKRPDEISQI LAQSQGSITLKIIPATQEEDR 240 MUPP1 domain 5 2104784 WEAGIQHIELEKGSKGLGFSILDYQDPIDPASTVIIIRSLVP GGIAEKDGRLLPGDRLMFVNDVNLENSSLEEAVEALKG APSGTVRIGVAKPLPLSPEE 241 MUPP1 domain 12 2104784 LQGLRTVEMKKGPTDSLGISIAGGVGSPLGDVPIFIAMMH PTGVAAQTQKLRVGDRIVTICGTSTEGMTHTQAVNLLKN ASGSIEMQVVAGGDVSV 242 MUPP1 domain 2 2104784 PVHWQHMETIELVNDGSGLGFGIIGGKATGVIVKTILPGG VADQHGRLCSGDHILKIGDTDLAGMSSEQVAQVLRQCG NRVKLMIARGAIEERTAPT 243 MUPP1 domain 3 2104784 QESETFDVELTKNVQGLGITIAGYIGDKKLEPSGIFVKSIT KSSAVEHDGRIQIGDQIIAVDGTNLQGFTNQQAVEVLRH TGQTVLLTLMRRGMKQEA 244 MUPP1 domain 11 2104784 KEEEVCDTLTIELQKKPGKGLGLSIVGKRNDTGVFVSDIV KGGIADADGRLMQGDQILMVNGEDVRNATQEAVAALL KCSLGTVTLEVGRIKAGPFHS 245 MUPP1 domain 8 2104784 LTGELHMIELEKGHSGLGLSLAGNKDRSRMSVFIVGIDPN GAAGKDGRLQIADELLEINGQILYGRSHQNASSIIKCAPS KVKIIFIRNKDAVNQ 246 MUPP1 domain 13 2104784 LGPPQCKSITLERGPDGLGFSIVGGYGSPHGDLPIYVKTVF AKGAASEDGRLKRGDQIIAVNGQSLEGVTHEEAVAILKR TKGTVTLMVLS 247 MUPP1 domain 6 2104784 RNVSKESFERTINIAKGNSSLGMTVSANKDGLGMIVRSII HGGAISRDGRIAIGDCILSINEESTISVTNAQARAMLRRHS LIGPDIKITYVPAEHLEE 248 MUPP1 domain 10 2104784 LPGCETTIEISKGRTGLGLSIVGGSDTLLGAIIIHEVYEEGA ACKDGRLWAGDQILEVNGIDLRKATHDEAINVLRQTPQR VRLTLYRDEAPYKE 249 MUPP1 domain 7 2104784 LNWNQPRRVELWREPSKSLGISIVGGRGMGSRLSNGEV MRGIFIKHVLEDSPAGKNGTLKPGDRIVEVDGMDLRDAS HEQAVEAIRKAGNPVVFMVQSIINRPRKSPLPSLL 250 MUPP1 domain 9 2104784 LSSFKNVQHLELPKDQGGLGIAISEEDTLSGVIIKSLTEHG VAATDGRLKVGDQILAVDDEIVVGYPIEKFISLLKTAKM TVKLTIHAENPDSQ 251 MUPP1 domain 1 2104784 QGRHVEVFELLKPPSGGLGFSVVGLRSENRGELGIFVQEI QEGSVAHRDGRLKETDQILAINGQALDQTITHQQAISILQ KAKDTVQLVIARGSLPQLV 252 MUPP1 domain 4 2104784 LNYEIVVAHVSKFSENSGLGISLEATVGHHFIRSVLPEGPV GHSGKLFSGDELLEVNGITLLGENHQDVVNILKELPIEVT MVCCRRTVPPT 253 NeDLG domain 2 10863920 ITLLKGPKGLGFSIAGGIGNQHIPGDNSIYITKIIEGGAAQK DGRLQIGDRLLAVNNTNLQDVRHEEAVASLKNTSDMVY LKVAKPGSLE 254 NeDLG domain 1 10863920 IQYEEIVLERGNSGLGFSIAGGIDNPHVPDDPGIFITKIIPGG AAAMDGRLGVNDCVLRVNEVEVSEVVHSRAVEALKEA GPVVRLVVRRRQN 255 NeDLG domain 3 10863920 ILLHKGSTGLGFNIVGGEDGEGIFVSFILAGGPADLSGELR RGDRILSVNGVNLRNATHEQAAAALKRAGQSVTIVAQY RPEEYSRFESKIHDLREQMMNSSMSSGSGSLRTSEKRSLE 256 NeDLG domains 1 10863920 YEEIVLERGNSGLGFSIAGGIDNPHVPDDPGIFITKIIPGGA and 2 AAMDGRLGVNDCVLRVNEVEVSEVVHSRAVEALKEAG PVVRLVVRRRQPPPETIMEVNLLKGPKGLGFSIAGGIGNQ HIPGDNSIYITKIIEGGAAQKDGRLQIGDRLLAVNNTNLQ DVRHEEAVASLKNTSDMVYLKVAKPGSL 257 Neurabin II domain 1 AJ401189 RVERLELFPVELEKDSEGLGISIIGMGAGADMGLEKLGIF VKTVTEGGAAHRDGRIQVNDLLVEVDGTSLVGVTQSFA ASVLRNTKGRVRCRFMIGRERPGEQSEV 258 NOS1 domain 1 642525 QPNVISVRLFKRKVGGLGFLVKERVSKPPVIISDLIRGGA AEQSGLIQAGDIILAVNGRPLVDLSYDSALEVLRGIASET HVVLILRGPE 259 novel PDZ gene 7228177 PSDTSSEDGVRRIVHLYTTSDDFCLGFNIRGGKEFGLGIY domain 2 VSKVDHGGLAEENGIKVGDQVLAANGVRFDDISHSQAV EVLKGQTHIMLTIKETGRYPAYKEM 260 novel PDZ gene 7228177 EANSDESDIIHSVRVEKSPAGRLGFSVRGGSEHGLGIFVS domain 1 KVEEGSSAERAGLCVGDKITEVNGLSLESTTMGSAVKVL TSSSRLHMMVRRMGRVPGIKFSKEK 261 novel serine 1621243 DKIKKFLTESHDRQAKGKAITKKKYIGIRMMSLTSSKAK protease domain 1 ELKDRHRDFPDVISGAYIIEVIPDTPAEAGGLKENDVIISIN GQSVVSANDVSDVIKRESTLNMVVRRGNEDIMITV 262 Numb BP domain 2 AK056823 YRPRDDSFHVILNKSSPEEQLGIKLVRKVDEPGVFIFNAL DGGVAYRHGQLEENDRVLAINGHDLRYGSPESAAHLIQ ASERRVHLVVSRQVRQRSPD 263 Numb BP domain 3 AK056823 PTITCHEKVVNIQKDPGESLGMTVAGGASHREWDLPIYVI SVEPGGVISRDGRIKTGDILLNVDGVELTEVSRSEAVALL KRTSSSIVLKALEVKEYEPQ 264 Numb BP domain 1 AK056823 PDGEITSIKINRVDPSESLSIRLVGGSETPLVHIIIQHIYRDG VIARDGRLLPRDIILKVNGMDISNVPHNYAVRLLRQPCQ VLWLTVMREQKFRSR 265 Numb BP domain 4 AK056823 PRCLYNCKDIVLRRNTAGSLGFCIVGGYEEYNGNKPFFIK SIVEGTPAYNDGRIRCGDILLAVNGRSTSGMIHACLARLL KELKGRITLTIVSWPGTFL 266 outer membrane 7023825 LLTEEEINLTRGPSGLGFNIVGGTDQQYVSNDSGIYVSRIK domain 1 ENGAAALDGRLQEGDKILSVNGQDLKNLLHQDAVDLFR NAGYAVSLRVQHRLQVQNGIHS 267 p55T domain 1 12733367 PVDAIRILGIHKRAGEPLGVTFRVENNDLVIARILHGGMI DRQGLLHVGDIIKEVNGHEVGNNPKELQELLKNISGSVT LKILPSYRDTITPQQ 268 PAR3 domain 2 8037914 GKRLNIQLKKGTEGLGFSITSRDVTIGGSAPIYVKNILPRG AAIQDGRLKAGDRLIEVNGVDLVGKSQEEVVSLLRSTKM EGTVSLLVFRQEDA 269 PAR3 domain 1 8037914 IPNFSLDDMVKLVEVPNDGGPLGIHVVPFSARGGRTLGL LVKRLEKGGKAEHENLFRENDCIVRINDGDLRNRRFEQA QHMFRQAMRTPIIWFHVVPAANKEQYEQ 270 PAR3 domain 3 8037914 PREFLTFEVPLNDSGSAGLGVSVKGNRSKENHADLGIFV KSIINGGAASKDGRLRVNDQLIAVNGESLLGKTNQDAME TLRRSMSTEGNKRGMIQLIVASRISKCNELKSNSS 271 PAR3L domain 2 18874467 ISNKNAKKIKIDLKKGPEGLGFTVVTRDSSIHGPGPIFVKN ILPKGAAIKDGRLQSGDRILEVNGRDVTGRTQEELVAML RSTKQGETASLVIARQEGH 272 PAR3L domain 3 18874467 ITSEQLTFEIPLNDSGSAGLGVSLKGNKSRETGTDLGIFIKS IIHGGAAFKDGRLRMNDQLIAVNGESLLGKSNHEAMETL RRSMSMEGNIRGMIQLVILRRPERP 273 PAR3L domain 1 18874467 IPRTKDTLSDMTRTVEISGEGGPLGIHVVPFFSSLSGRILGL FIRGIEDNSRSKREGLFHENECIVKINNVDLVDKTFAQAQ DVFRQAMKSPSVLLHVLPPQNR 274 PAR6 domain 1 2613011 PETHRRVRLHKHGSDRPLGFYIRDGMSVRVAPQGLERVP GIFISRLVRGGLAESTGLLAVSDEILEVNGIEVAGKTLDQ VTDMMVANSHNLIVTVKPANQRNNV 275 PAR6 beta domain 1 1353716 IPVSSIIDVDILPETHRRVRLYKYGTEKPLGFYIRDGSSVR VTPHGLEKVPGIFISRLVPGGLAQSTGLLAVNDEVLEVNG IEVSGKSLDQVTDMMIANSRNLIITVRPANQRNNRIHRD 276 PAR6 GAMMA 13537118 IDVDLVPETHRRVRLHRHGCEKPLGFYIRDGASVRVTPH domain 1 GLEKVPGIFISRMVPGGLAESTGLLAVNDEVLEVNGIEVA GKTLDQVTDMMIANSHNLIVTVKPANQRNNVV 277 PDZ-73 domain 3 5031978 PEQIMGKDVRLLRIKKEGSLDLALEGGVDSPIGKVVVSA VYERGAAERHGGIVKGDEIMAINGKIVTDYTLAEADAAL QKAWNQGGDWIDLVVAVCPPKEYDD 278 PDZ-73 domain 2 5031978 IPGNRENKEKKVFISLVGSRGLGCSISSGPIQKPGIFISHVK PGSLSAEVGLEIGDQIVEVNGVDFSNLDHKEAVNVLKSS RSLTISIVAAAGRELFMTDEF 279 PDZ-73 domain 1 5031978 RSRKLKEVRLDRLHPEGLGLSVRGGLEFGCGLFISHLIKG GQADSVGLQVGDEIVRINGYSISSCTHEEVINLIRTKKTVS IKVRHIGLIPVKSSPDEFH 280 PDZK1 domain 2 2944188 RLCYLVKEGGSYGFSLKTVQGKKGVYMTDITPQGVAMR AGVLADDHLIEVNGENVEDASHEEVVEKVKKSGSRVMF LLVDKETDKREFIVTD 281 PDZK1 domain 3 2944188 QFKRETASLKLLPHQPRIVEMKKGSNGYGFYLRAGSEQK GQIIKDIDSGSPAEEAGLKNNDLVVAVNGESVETLDHDS VVEMIRKGGDQTSLLVVDKETDNMYRLAEFIVTD 282 PDZK1 domains 2 2944188 RLCYLVKEGGSYGFSLKTVQGKKGVYMTDITPQGVAMR and 3 and 4 AGVLADDHLIEVNGENVEDASHEKVVEKVKKSGSRVMF LLVDKETDKRHVEQKIQFKRETASLKLLPHQPRIVEMKK GSNGYGFYLRAGSEQKGQIIKDIDSGSPAEEAGLKNNDL VVAVNGESVETLDHDSVVEMIRKGGDQTSLLVVDKETD NMYRLAHFSPFLYYQSQELPNGSVKEAPAPTPTSLEVSSP PDTTEEVDHKPKLCRLAKGENGYGFHLNAIRGLPGSFIKE VQKGGPADLAGLEDEDVIIEVNGVNVLDEPYEKVVDRIQ SSGKNVTLLVCGK

283 PDZK1 domain 4 2944188 PDTTEEVDHKPKLCRLAKGENGYGFHLNAIRGLPGSFIKE VQKGGPADLAGLEDEDVIIEVNGVNVLDEPYEKVVDRIQ SSGKNVTLLVGKNSS 284 PDZK1 domain 1 2944188 LTSTFNPRECKLSKQEGQNYGFFLRIEKDTEGHLVRVVE KCSPAEKAGLQDGDRVLRINGVFVDKEEHMQVVDLVRK SGNSVTLLVLDGDSYEKAGSHEPS 285 PICK1 domain 1 4678411 LGIPTVPGKVTLQKDAQNLIGISIGGGAQYCPCLYIVQVF DNTPAALDGTVAAGDEITGVNGRSIKGKTKVEVAKMIQE VKGEVTIHYNKLQADPKQGM 286 PIST domain 1 98374330 SQGVGPIRKVLLLKEDHEGLGISITGGKEHGVPILISEIHPG QPADRCGGLHVGDAILAVNGVNLRDTKHKEAVTILSQQ RGEIEFEVVYVAPEVDSD 287 prIL16 domain 2 1478492 TAEATVCTVTLEKMSAGLGFSLEGGKGSLHGDKPLTINRI FKGAASEQSETVQPGDEILQLGGTAMQGLTRFEAWNIIK ALPDGPVTIVIRRKSLQSK 288 prIL16 domain 1 1478492 IHVTILHKEEGAGLGFSLAGGADLENKVITVHRVFPNGLA SQEGTIQKGNEVLSINGKSLKGTTHHDALAILRQAREPRQ AVIVTRKLTPEEFIVTD 289 prIL16 domains 1 1478492 IHVTILHKEEGAGLGFSLAGGADLENKVITVHRVFPNGLA and 2 SQEGTIQKGNEVLSINGKSLKGTTHHDALAILRQAREPRQ AVIVTRKLTPEAMPDLNSSTDSAASASAASDVSVESTAE ATVCTVTLEKMSAGLGFSLEGGKGSLHGDKPLTINRIFK GAASEQSETVQPGDEILQLGGTAMQGLTRFEAWNIIKAL PDGPVTIVIRRKSLQSK 290 PSAP domain 1 6409315 IREAKYSGVLSSIGKIFKEEGLLGFFVGLIPHLLGDVVFLW GCNLLAHFINAYLVDDSVSDTPGGLGNDQNPGSQFSQAL AIRSYTKFVMGIAVSMLTYPFLLVGDLMAVNNCGLQAG LPPYSPVFKSWIHCWKYLSVQGQLFRGSSLLFRRVSSGSC FALE 291 PSD95 domains 1 3318652 EGEMEYEEITLERGNSGLGFSIAGGTDNPHIGDDPSIFITKI and 2 and 3 IPGGAAAQDGRLRVNDSILFVNEVDVREVTHSAAVEALK EAGSIVRLYVMRRKPPAEKVMEIKLIKGPKGLGFSIAGGV GNQHIPGDNSIYVTKIIEGGAAHKDGRLQIGDKILAVNSV GLEDVMHEDAVAALKNTYDVVYLKVAKPSNAYLSDSY APPDITTSYSQHLDNEISHSSYLGTDYPTAMTPTSPRRYSP VAKDLLGEEDIPREPRIVIHRGSTGLGFNIVGGEDGEGIF ISFILAGGPADLSGELRKGDQILSVNGVDLRNASHEQAAI ALKNAGQTVTIIAQYKPE 292 PSD95 domain 2 3318652 HVMRRKPPAEKVMEIKLIKGPKGLGFSIAGGVGNQHIPG DNSIYVTKIIEGGAAHKDGRLQIGDKILAVNSVGLEDVM HEDAVAALKNTYDVVYLKVAKPSNAYL 293 PSD95 domain 3 3318652 REDIPREPRRIVIHRGSTGLGFNIVGGEDGEGIFISFILAGG PADLSGELRKGDQILSVNGVDLRNASHEQAAIALKNAGQ TVTIIAQYKPEFIVTD 294 PSD95 domain 1 3318652 LEYEeITLERGNSGLGFSIAGGTDNPHIGDDPSIFITKIIPGG AAAQDGRLRVNDSILFVNEVDVREVTHSAAVEALKEAG SIVRLYVMRRKPPAENSS 295 PSMD9 domain 1 9184389 RDMAEAHKEAMSRKLGQSESQGPPRAFAKVNSISPGSPA SIAGLQVDDEIVEFGSVNTQNFQSLHNIGSVVQHSEGALA PTILLSVSM 296 PTN-3 domain 1 179912 QNDNGDSYLVLIRITPDEDGKFGFNLKGGVDQKMPLVVS RINPESPADTCIPKLNEGDQIVLINGRDISEHTHDQVVMFI KASRESHSRELALVIRRRAVRS 297 PTN-4 domain 1 190747 IRMKPDENGRFGFNVKGGYDQKMPVIVSRVAPGTPADL CVPRLNEGDQVVLINGRDIAEHTHDQVVLFIKASCERHS GELMLLVRPNA 298 PTPL1 domain 2 515030 GDIFEVELAKNDNSLGISVTGGVNTSVRHGGIYVKAVIPQ GAAESDGRIHKGDRVLAVNGVSLEGATHKQAVETLRNT GQVVHLLLEKGQSPTSK 299 PTPL1 domain 1 515030 PEREITLVNLKKDAKYGLGFQIIGGEKMGRLDLGIFISSVA PGGPADFHGCLKPGDRLISVNSVSLEGVSHHAAIEILQNA PEDVTLVISQPKEKISKVPSTPVHL 300 PTPL1 domain 4 515030 ELEVELLITLIKSEKASLGFTVTKGNQRIGCYVHDVIQDP AKSDGRLKPGDRLIKVNDTDVTNMTHTDAVNLLRAASK TVRLVIGRVLELPRIPMLPH 301 PTPL1 domain 3 515030 TEENTFEVKLFKNSSGLGFSFSREDNLIPEQINASIVRVKK LFAGQPAAESGKIDVGDVILKVNGASLKGLSQQEVISALR GTAPEVFLLLCRPPPGVLPEIDT 302 PTPL1 domain 5 515030 MLPHLLPDITLTCNKEELGFSLCGGHDSLYQVVYISDINP RSVAAIEGNLQLLDVIHYVNGVSTQGMTLEEVNRALDM SLPSLVLKATRNDLPV 303 RGS 3 domain 1 18644735 VCSERRYRQITIPRGKDGFGFTICCDSPVRVQAVDSGGPA ERAGLQQLDTVLQLNERPVEHWKCVELAHEIRSCPSEIIL LVWRMVPQVKPG 304 RGS12 domain 1 3290015 RPSPPRVRSVEVARGRAGYGFTLSGQAPCVLSCVMRGSP ADFVGLRAGDQILAVNEINVKKASHEDVVKLIGKCSGVL HMVIAEGVGRFESCS 305 Rho-GAP 10 50345878 SEDETFSWPGPKTVTLKRTSQGFGFTLRHFIVYPPESAIQF domain 1 SYKDEENGNRGGKQRNRLEPMDTIFVKQVKEGGPAFEA GLCTGDRIIKVNGESVIGKTYSQVIALIQNSDTTLELSVMP KDED 306 Rhophilin domain 1 AY082588 SAKNRWRLVGPVHLTRGEGGFGLTLRGDSPVLIAAVIPG SQAAAAGLKEGDYIVSVNGQPCRWWRHAEVVTELKAA GEAGASLQVVSLLPSSRLPS 307 Rhophilin-like AF268032 ISFSANKRWTPPRSIRFTAEEGDLGFTLRGNAPVQVHFLD domain 1 PYCSASVAGAREGDYIVSIQLVDCKWLTLSEVMKLLKSF GEDEIEMKVVSLLDSTSSMHNKSAT 308 RIM2 domain 1 12734165 TLNEEHSHSDKHPVTWQPSKDGDRLIGRILLNKRLKDGS VPRDSGAMLGLKVVGGKMTESGRLCAFITKVKKGSLAD TVGHLRPGDEVLEWNGRLLQGATFEEVYNIILESKPEPQ VELVVSRPIG 309 SEMCAP 3 domain 2 5889526 QEMDREELELEEVDLYRMNSQDKLGLTVCYRTDDEDDI GIYISEIDPNSIAAKDGRIREGDRIIQINGIEVQNREEAVAL LTSEENKNFSLLIARPELQLD 310 SEMCAP 3 domain 1 5889526 QGEETKSLTLVLHRDSGSLGFNIIGGRPSVDNHDGSSSEGI FVSKIVDSGPAAKEGGLQIHDRIIEVNGRDLSRATHDQAV EAFKTAKEPIVVQVLRRTPRTKMFTP 311 semcap2 domain 1 7019938 ILAHVKGIEKEVNVYKSEDSLGLTITDNGVGYAFIKRIKD GGVIDSVKTICVGDHIESINGENIVGWRHYDVAKKLKEL KKEELFTMKLIEPKKAFEI 312 serine protease 2738914 RGEKKNS SSGISGSQRRYIGVMMLTLSPSILAELQLREPSF domain 1 PDVQHGVLIHKVILGSPAHRAGLRPGDVILAIGEQMVQN AEDVYEAVRTQSQLAVQIRRGRETLTLYV 313 Shank 1 domain 1 6049185 ILEEKTVVLQKKDNEGFGFVLRGAKADTPIEEFTPTPAFP ALQYLESVDEGGVAWQAGLRTGDFLIEVNNENVVKVGH RQVVNMIRQGGNHLVLKVVTVTRNLDPDDNSS 314 Shank 2 domain 1 7025450 ILKEKTVLLQKKDSEGFGFVLRGAKAQTPIEEFTPTPAFP ALQYLESVDEGGVAWRAGLRMGDFLIEVNGQNVVKVG HRQVVNMIRQGGNTLMVKVVMVTRHPDMDEAVQNSS 315 Shank 3 domain 1 * SDYVIDDKVAVLQKRDHEGFGFVLRGAKAETPIEEFTPTP AFPALQYLESVDVEGVAWRAGLRTGDFLIEVNGVNVVK VGHKQVVALIRQGGNRLVMKVVSVTRKPEEDG 316 sim to lig of numb 22477649 SNSPREEIFQVALHKRDSGEQLGIKLVRRTDEPGVFILDLL px2 domain 2 EGGLAAQDGRLSSNDRVLAINGHDLKYGTPELAAQIIQA SGERVNLTIARPGKPQPG 317 sim to lig of numb 22477649 IQCVTCQEKHITVKKEPHESLGMTVAGGRGSKSGELPIFV px2 domain 3 TSVPPHGCLARDGRIKRGDVLLNINGIDLTNLSHSEAVA MLKASAASPAVALKALEVQIVEEAT 318 Similar to 14286261 MGLGVSAEQPAGGAEGFHLHGVQENSPAQQAGLEPYFD GRASP65 domain 1 FIITIGHSRLNKENDTLKALLKANVEKPVKLEVFNMKTM RVREVEVVPSNMWGGQGLLGASVRFCSFRRASE 319 Similar to 14286261 RASEQVWHVLDVEPSSPAALAGLRPYTDYVVGSDQILQE GRASP65 domain 2 SEDFFTLIESHEGKPLKLMVYNSKSDSCRESGMWHWLW VSTPDPNSAPQLPQEATWHPTTFCSTTWCPTT 320 Similar to Protein- 21595065 ISVTDGPKFEVKLKKNANGLGFSFVQMEKESCSHLKSDL Tyrosine- VRIKRLFPGQPAEENGAIAAGDIILAVNGRSTEGLIFQEVL Phosphatase HLLRGAPQEVTLLLCRPPPGA Homolog domain 1 321 SIP1 domain 1 2047327 QPEPLRPRLCRLVRGEQGYGFHLHGEKGRRGQFIRRVEP GSPAEAAALRAGDRLVEVNGVNVEGETHHQVVQRIKAV EGQTRLLVVDQETDEELRRRNSS 322 SIP1 domain 2 2047327 PLRELRPRLCHLRKGPQGYGFNLHSDKSRPGQYIRSVDP GSPAARSGLRAQDRLIEVNGQNVEGLRHAEVVASIKARE DEARLLVVDPETDEHFKRNSS 323 SITAC 18 domain 1 8886071 PGVREIHLCKDERGKTGLRLRKVDQGLFVQLVQANTPAS LVGLRFGDQLLQIDGRDCAGWSSHKAHQVVKKASGDKI VVVVRDRPFQRTVTM 324 SITAC 18 domain 2 8886071 PFQRTVTMHKDSMGHVGFVIKKGKIVSLVKGSSAARNG LLTNHYVCEVDGQNVIGLKDKKIMEILATAGNVVTLTIIP SVIYEHIVEFIV 325 SNPC IIa domain 1 20809633 SLERPRFCLLSKEEGKSFGFHLQQELGRAGHVVCRVDPG TSAQRQGLQEGDRILAVNNDVVEHEDYAVVVRRIRASSP RVLLTVLARHAHDVARAQ 326 SYNTENIN domain 2 2795862 LRDRPFERTITMHKDSTGHVGFIFKNGKITSIVKDSSAAR NGLLTEHNICEINGQNVIGLKDSQIADILSTSGTVVTITIMP AFIFEHMNSS 327 SYNTENIN domain 1 2795862 LEIKQGLREVILCKDQDGKIGLRLKSIDNGIFVQLVQANSP ASLVGLRFGDQVLQINGENCAGWSSDKAHKVLKQAFGE KITMRIHRD 328 Syntrophin 1 alpha 1145727 QRRRVTVRKADAGGLGISIKGGRENKMPILISKTFKGLAA domain 1 DQTEALFVGDAILSVNGEDLSSATHDEAVQVLKKTGKEV VLEVKYMKDVSPYFK 329 Syntrophin beta 2 476700 PVRRVRVVKQEAGGLGISIKGGRENRMPILISKIFPGLAA domain 1 DQSRALRLGDAILSVNGTDLRQATHDQAVQALKRAGKE VLLEVKFIRE 330 Syntrophin gamma 9507162 EPFYSGERTVTIRRQTVGGFGLSIKGGAEHNLPVVVSKISK 1 domain 1 EQRAELSGLLFIGDAILQINGINVRKCRHEEVVQVLRNAG EEVTLTVSFLKRAPAFLKL 331 Syntrophin gamma 9507164 SHQGRNRRTVTLRRQPVGGLGLSIKGGSEHNVPVVISKIF 2 domain 1 EDQAADQTGMLFVGDAVLQVNGIHVENATHEEVVHLLR NAGDEVTITVEYLREAPAFLK 332 TAX2-like protein 3253116 RGETKEVEVTKTEDALGLTITDNGAGYAFIKRIKEGSIINR domain 1 IEAVCVGDSIEAINDHSIVGCRHYEVAKMLRELPKSQPFT LRLVQPKRAF 333 TIAM1 domain 1 4507500 HSIHIEKSDTAADTYGFSLSSVEEDGIRRLYVNSVKETGL ASKKGLKAGDEILEINNRAADALNSSMLKDFLSQPSLGL LVRTYPELE 334 TIAM2 domain 1 6912703 PLNVYDVQLTKTGSVCDFGFAVTAQVDERQHLSRIFISD VLPDGLAYGEGLRKGNEIMTLNGEAVSDLDLKQMEALF SEKSVGLTLIARPPDTKATL 335 TIP1 domain 1 2613001 QRVEIHKLRQGENLILGFSIGGGIDQDPSQNPFSEDKTDK GIYVTRVSEGGPAEIAGLQIGDKIMQVNGWDMTMVTHD QARKRLTKRSEEVVRLLVTRQSLQK 336 TIP2 domain 1 2613003 RKEVEVFKSEDALGLTITDNGAGYAFIKRIKEGSVIDHIHL ISVGDMIEAINGQSLLGCRHYEVARLLKELPRGRTFTLKL TEPRK 337 TIP33 domain 1 2613007 HSHPRVVELPKTDEGLGFNVMGGKEQNSPIYISRIIPGGV AERHGGLKRGDQLLSVNGVSVEGEHHEKAVELLKAAKD SVKLVVRYTPKVL 338 TIP43 domain 1 2613011 LSNQKRGVKVLKQELGGLGISIKGGKENKMPILISKIFKG LAADQTQALYVGDAILSVNGADLRDATHDEAVQALKRA GKEVLLEVKYMREATPYVK 339 Unknown PDZ 22382223 IQRSSIKTVELIKGNLQSVGLTLRLVQSTDGYAGHVIIETV domain 1 APNSPAAIADLQRGDRLIAIGGVKITSTLQVLKLIKQAGD RVLVYYERPVGQSNQGA 340 Vartul domain 1 1469875 ILTLTILRQTGGLGISIAGGKGSTPYKGDDEGIFISRVSEEG PAARAGVRVGDKLLEVNGVALQGAEHHEAVEALRGAG TAVQMRVWRERMVEPENAEFIVTD 341 Vartul domain 4 1469875 RELCIQKAPGERLGISIRGGARGHAGNPRDPTDEGIFISKV SPTGAAGRDGRLRVGLRLLEVNQQSLLGLTHGEAVQLL RSVGDTLTVLVCDGFEASTDAALEVS

342 Vartul domain 3 1469875 LEGPYPVEEIRLPRAGGPLGLSIVGGSDHSSHPFGVQEPG VFISKVLPRGLAARSGLRVGDRILAVNGQDVRDATHQEA VSALLRPCLELSLLVRRDPAEFIVTD 343 Vartul domain 2 1469875 PLRQRHVACLARSERGLGFSIAGGKGSTPYRAGDAGIFVS RIAEGGAAHRAGTLQVGDRVLSINGVDVTEARHDHAVS LLTAASPTIALLLEREAGG 344 Vartul domains 1 1469875 TLTILRQTGGLGISIAGGKGSTPYKGDDEGIFISRVSEEGP and 2 AARAGVRVGDKLLEGIFVSRIAEGGAAHRAGTLQVGDR VLSINGVDVTEARHDHAVSLLTAASPTIALLLERE 345 X-11 beta domain 2 3005559 IPPVTTVLIKRPDLKYQLGFSVQNGIICSLMRGGIAERGGV RVGHRIIEINGQSVVATAHEKIVQALSNSVGEIHMKTMPA AMFRLLTGQENSSL 346 X-11 beta domain 1 3005559 IHFSNSENCKELQLEKHKGEILGVVVVESGWGSLLPTVIL ANMMNGGPAARSGKLSIGDQIMSINGTSLVGLPLATCQG IIKGLKNQTQVKLNIVSCPPVTFVLIKRNSS 347 ZO-1 domain 1 292937 IWEQHTVTLHRAPGFGFGIAISGGRDNPHFQSGETSIVISD VLKGGPAEGQLQENDRVAMVNGVSMDNVEHAFAVQQL RKSGKNAKITIRRKKKVQIPNSS 348 ZO-1 domain 2 292937 ISSQPAKPTKVTLVKSRKNEEYGLRLASHIFVKEISQDSLA ARDGNIQEGDVVLKINGTVTENMSLTDAKTLIERSKGKL KMVVQRDRATLLNSS 349 ZO-1 domain 3 292937 IRMKLVKFRKGDSVGLRLAGGNDVGIFVAGVLEDSPAA KEGLEEGDQILRVNNVDFTNIIREEAVLFLLDLPKGEEVTI LAQKKKDVFSN 350 ZO-2 domain 1 12734763 IQHTVTLHRAPGFGFGIAISGGRDNPHFQSGETSIVISDVL KGGPAEGQLQENDRVAMVNGVSMDNVEHAFAVQQLRK SGKNAKITIRRKKKVQIPNSS 351 ZO-2 domain 3 12734763 HAPNTKMVRFKKGDSVGLRLAGGNDVGIFVAGIQEGTS AEQEGLQEGDQILKVNTQDFRGLVREDAVLYLLEIPKGE MVTILAQSRADVY 352 ZO-2 domain 2 12734763 RVLLMKSRANEEYGLRLGSQIFVKEMTRTGLATKDGNL HEGDIILKINGTVTENMSLTDARKLIEKSRGKLQLVVLRDS 353 ZO-3 domain 3 10092690 RGYSPDTRVVRFLKGKSIGLRLAGGNDVGIFVSGVQAGS PADGQGIQEGDQILQVNDVPFQNLTREEAVQFLLGLPPG EEMELVTQRKQDIFWKMVQSEFIVTD 354 ZO-3 domain 1 10092690 IPGNSTIWEQHTATLSKDPRRGFGIAISGGRDRPGGSMVV SDVVPGGPAEGRLQTGDHIVMVNGVSMENATSAFAIQIL KTCTKMANITVKRPRRIHLPAEFIVTD 355 ZO-3 domain 2 10092690 QDVQMKPVKSVLVKRRDSEEFGVKLGSQIFIKHITDSGL AARHRGLQEGDLILQINGVSSQNLSLNDTRRLIEKSEGKL SLLVLRDRGQFLVNIPNSS *: No GI number for this PDZ domain containing protein as it was computer cloned using rat Shank3 sequence against human genomic clone AC000036 and in silico spliced together nucleotides 6400-6496, 6985-7109, 7211-7400 to create hypothetical human Shank3.

[0096]Methods for Detecting the Presence of an Oncogenic HPV E6 Protein in a Sample

[0097]The invention provides a method of detecting the presence of an oncogenic HPV E6 protein in a sample. In general, the method involves contacting a biological sample containing or potentially containing an oncogenic HPV E6 protein with a PDZ domain polypeptide and detecting any binding of the oncogenic HPV E6 protein in said sample to the PDZ domain polypeptide using a subject antibody. In alternative embodiments, a sample may be contacted with a subject antibody, and the presence of the E6 protein may be detected using the PDZ domain polypeptide. In most embodiments, binding of an oncogenic HPV E6 protein to the PDZ domain polypeptide and a subject antibody indicates the presence of an oncogenic HPV E6 protein in the sample.

[0098]Biological samples to be analyzed using the methods of the invention may be obtained from any mammal, e.g., a human or a non-human animal model of HPV. In many embodiments, the biological sample is obtained from a living subject.

[0099]In some embodiments, the subject from whom the sample is obtained is apparently healthy, where the analysis is performed as a part of routine screening. In other embodiments, the subject is one who is susceptible to HPV, (e.g., as determined by family history; exposure to certain environmental factors; etc.). In other embodiments, the subject has symptoms of HPV (e.g., cervical warts, or the like). In other embodiments, the subject has been provisionally diagnosed as having HPV (e.g. as determined by other tests based on e.g., PCR).

[0100]The biological sample may be derived from any tissue, organ or group of cells of the subject. In some embodiments a cervical scrape, biopsy, or lavage is obtained from a subject. In other embodiments, the sample is a blood or urine sample.

[0101]In some embodiments, the biological sample is processed, e.g., to remove certain components that may interfere with an assay method of the invention, using methods that are standard in the art. In some embodiments, the biological sample is processed to enrich for proteins, e.g., by salt precipitation, and the like. In certain embodiments, the sample is processed in the presence proteasome inhibitor to inhibit degradation of the E6 protein.

[0102]In the assay methods of the invention, in some embodiments, the level of E6 protein in a sample may be quantified and/or compared to controls. Suitable control samples are from individuals known to be healthy, e.g., individuals known not to have HPV. Control samples can be from individuals genetically related to the subject being tested, but can also be from genetically unrelated individuals. A suitable control sample also includes a sample from an individual taken at a time point earlier than the time point at which the test sample is taken, e.g., a biological sample taken from the individual prior to exhibiting possible symptoms of HPV.

[0103]In certain embodiments, a sample is contacted to a solid support-bound PDZ domain polypeptide under conditions suitable for binding of the PDZ domain polypeptide to any PL proteins in the sample, and, after separation of unbound sample proteins from the bound proteins, the bound proteins are detected using the subject antibody using known methods.

[0104]Kits

[0105]The present invention also includes kits for carrying out the methods of the invention. A subject kit usually contains a subject antibody. In many embodiments, the kits contain a first and second binding partner, where the first binding partner is a PDZ domain polypeptide and the second binding partner is a subject antibody. In some embodiments, the second binding partner is labeled with a detectable label. In other embodiments, a secondary labeling component, such as a detectably labeled secondary antibody, is included. In some embodiments, a subject kit further comprises a means, such as a device or a system, for isolating oncogenic HPV E6 from the sample. The kit may optionally contain proteasome inhibitor.

[0106]A subject kit can further include, if desired, one or more of various conventional components, such as, for example, containers with one or more buffers, detection reagents or antibodies. Printed instructions, either as inserts or as labels, indicating quantities of the components to be used and guidelines for their use, can also be included in the kit. In the present disclosure it should be understood that the specified materials and conditions are important in practicing the invention but that unspecified materials and conditions are not excluded so long as they do not prevent the benefits of the invention from being realized. Exemplary embodiments of the diagnostic methods of the invention are described above in detail.

[0107]In a subject kit, the oncogenic E6 detection reaction may be performed using an aqueous or solid substrate, where the kit may comprise reagents for use with several separation and detection platforms such as test strips, sandwich assays, etc. In many embodiments of the test strip kit, the test strip has bound thereto a PDZ domain polypeptide that specifically binds the PL domain of an oncogenic E6 protein and captures oncogenic E6 protein on the solid support. The kit usually comprises a subject antibody for detection, which is either directly or indirectly detectable, and which binds to the oncogenic E6 protein to allow its detection. Kits may also include components for conducting western blots (e.g., pre-made gels, membranes, transfer systems, etc.); components for carrying out ELISAs (e.g., 96-well plates); components for carrying out immunoprecipitation (e.g. protein A); columns, especially spin columns, for affinity or size separation of oncogenic E6 protein from a sample (e.g. gel filtration columns, PDZ domain polypeptide columns, size exclusion columns, membrane cut-off spin columns etc.).

[0108]Subject kits may also contain control samples containing oncogenic or non-oncogenic E6, and/or a dilution series of oncogenic E6, where the dilution series represents a range of appropriate standards with which a user of the kit can compare their results and estimate the level of oncogenic E6 in their sample. Such a dilution series may provide an estimation of the progression of any cancer in a patient. Fluorescence, color, or autoradiological film development results may also be compared to a standard curves of fluorescence, color or film density provided by the kit.

[0109]In addition to above-mentioned components, the subject kits typically further include instructions for using the components of the kit to practice the subject methods. The instructions for practicing the subject methods are generally recorded on a suitable recording medium. For example, the instructions may be printed on a substrate, such as paper or plastic, etc. As such, the instructions may be present in the kits as a package insert, in the labeling of the container of the kit or components thereof (i.e., associated with the packaging or subpackaging) etc. In other embodiments, the instructions are present as an electronic storage data file present on a suitable computer readable storage medium, e.g. CD-ROM, diskette, etc. In yet other embodiments, the actual instructions are not present in the kit, but means for obtaining the instructions from a remote source, e.g. via the interne, are provided. An example of this embodiment is a kit that includes a web address where the instructions can be viewed and/or from which the instructions can be downloaded. As with the instructions, this means for obtaining the instructions is recorded on a suitable substrate.

[0110]Also provided by the subject invention are kits including at least a computer readable medium including programming as discussed above and instructions. The instructions may include installation or setup directions. The instructions may include directions for use of the invention with options or combinations of options as described above. In certain embodiments, the instructions include both types of information.

[0111]The instructions are generally recorded on a suitable recording medium. For example, the instructions may be printed on a substrate, such as paper or plastic, etc. As such, the instructions may be present in the kits as a package insert, in the labeling of the container of the kit or components thereof (i.e., associated with the packaging or subpackaging), etc. In other embodiments, the instructions are present as an electronic storage data file present on a suitable computer readable storage medium, e.g., CD-ROM, diskette, etc, including the same medium on which the program is presented.

[0112]Utility

[0113]The antibodies and methods of the instant invention are useful for a variety of diagnostic analyses. The instant antibodies and methods are useful for diagnosing infection by an oncogenic strain of HPV in an individual; for determining the likelihood of having cancer; for determining a patient's response to treatment for HPV; for determining the severity of HPV infection in an individual; and for monitoring the progression of HPV in an individual. The antibodies and the methods of the instant invention are useful in the diagnosis of infection with an oncogenic or a non-oncogenic strain of HPV associated with cancer, including cervical, ovarian, breast, anus, penis, prostate, larynx and the buccal cavity, tonsils, nasal passage, skin, bladder, head and neck squamous-cell, occasional periungal carcinomas, as well as benign anogenital warts. The antibodies and the methods of the instant invention are useful in the diagnosis of infection with an oncogenic or a non-oncogenic strain of HPV associated with Netherton's syndrome, epidermolysis verruciformis, endometriosis, and other disorders. The antibodies and the methods of the instant invention are useful in the diagnosis of infection with an oncogenic or a non-oncogenic strain of HPVin adult women, adult men, fetuses, infants, children, and immunocompromised individuals.

[0114]The subject methods may generally be performed on biological samples from living subjects. A particularly advantageous feature of the invention is that the methods can simultaneously detect, in one reaction, several known oncogenic strains of HPV.

[0115]In particular embodiments, the antibodies of the invention may be employed in immunohistological examination of a sample.

EXAMPLES

[0116]The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the present invention, and are not intended to limit the scope of what the inventors regard as their invention nor are they intended to represent that the experiments below are all or the only experiments performed. Efforts have been made to ensure accuracy with respect to numbers used (e.g. amounts, temperature, etc.) but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is weight average molecular weight, temperature is in degrees Centigrade, and pressure is at or near atmospheric.

Example 1

Sequence Analysis of HPV E6 Proteins to Determine Oncogenic Potential

[0117]PDZ proteins are known to bind certain carboxyl-terminal sequences of proteins (PLs). PL sequences that bind PDZ domains are predictable, and have been described in greater detail in U.S. patent application Ser. Nos. 09/710,059, 09/724,553 and 09/688,017. One of the major classes of PL motifs is the set of proteins terminating in the sequences --X--(S/T)-X--(V/I/L). We have examined the C-terminal sequences of E6 proteins from a number of HPV strains. All of the strains determined to be oncogenic by the National Cancer Institute exhibit a consensus PDZ binding sequence. Those E6 proteins from papillomavirus strains that are not cancerous lack a sequence that would be predicted to bind to PDZ domains, thus suggesting that interaction with PDZ proteins is a prerequisite for causing cancer in humans. This correlation between presence of a PL and ability to cause cancer is 100% in the sequences examined (Table 3A). In theory, with the disclosed PL consensus sequences from the patents listed supra, new variants of HPVs can be assessed for their ability to bind PDZ proteins and oncogenicity can be predicted on the basis of whether a PL is present. Earlier this year, five new oncogenic strains of Human papillomavirus were identified and their E6 proteins sequenced. As predicted, these proteins all contain a PL consensus sequence (Table 3B).

TABLE-US-00003 TABLE 3A Correlation of E6 PDZ-ligands and oncogenicity HPV E6 C-terminal PL Seq ID strain sequence yes/no Oncogenic No HPV 4 GYCRNCIRKQ No No 33 HPV 11 WTTCMEDLLP No No 34 HPV 20 GICRLCKHFQ No No 35 HPV 24 KGLCRQCKQI No No 36 HPV 28 WLRCTVRIPQ No No 37 HPV 36 RQCKHFYNDW No No 38 HPV 48 CRNCISHEGR No No 39 HPV 50 CCRNCYEHEG No No 40 HPV 16 SSRTRRETQL Yes Yes 41 HPV 18 RLQRRRETQV Yes Yes 42 HPV 31 WRRPRTETQV Yes Yes 43 HPV 35 WKPTRRETEV Yes Yes 44 HPV 30 RRTLRRETQV Yes Yes 45 HPV 39 RRLTRRETQV Yes Yes 46 HPV 45 RLRRRRETQV Yes Yes 47 HPV 51 RLQRRNETQV Yes Yes 48 HPV 52 RLQRRRVTQV Yes Yes 49 HPV 56 TSREPRESTV Yes Yes 50 HPV 59 QRQARSETLV Yes Yes 51 HPV 58 RLQRRRQTQV Yes Yes 52 HPV 33 RLQRRRETAL Yes Yes 53 HPV 66 TSRQATESTV Yes Yes* 54 HPV 68 RRRTRQETQV Yes Yes 55 HPV 69 RRREATETQV Yes Yes 56 HPV 34 QCWRPSATVV Yes Yes 356 HPV 67 WRPQRTQTQV Yes Yes 357 HPV 70 RRRIRRETQV Yes Yes 358 Table 3A: E6 C-terminal sequences and oncogenicity: HPV variants are listed at the left. Sequences were identified from Genbank sequence records. PL Yes/No was defined by a match or non-match to the consenses determined by the inventors and by Songyang et al. -X-(S/T)-X-(V/I/L). Oncogenicity data collected from National Cancer Institute; Kawashima et al. (1986) J. Virol. 57: 688-692; Kirii et al. (1998) Virus Genes 17: 117-121; Forslund et al. (1996) J. Clin. Microbiol. 34: 802-809. *Only found in oncogenic strains co-transfected with other oncogenic proteins.

TABLE-US-00004 TABLE 3B Correlation of recently identified oncogenic E6 proteins HPV E6 C-terminal PL Seq strain sequence yes/no oncogenic ID No HPV 26 RPRRQTETQV Yes Yes 63 HPV 53 RHTTATESAV Yes Yes 64 HPV 66 TSRQATESTV Yes Yes 65 HPV 73 RCWRPSATVV Yes Yes 66 HPV 82 PPRQRSETQV Yes Yes 67 Table 3B: E6 C-terminal sequences and oncogenicity. HPV variants are listed at the left. Sequences were identified from Genbank sequence records. PL Yes/No was defined by a match or non-match to the consensus sequence: -X-(S/T)-X-(V/I/L). Oncogenicity data on new strains collected from N Engl J Med 2003; 348: 518-527.

[0118]These tables provide a classification of the HPV strains based on the sequence of the C-terminal four amino acids of the E6 protein encoded by the HPV genome. The 21 oncogenic strains of HPV fall into one of 11 classes (based on the C-terminal four amino acids), and HPV strains not specifically listed above may also fall into these classes. As such, it is desirable to detect HPV strains from all 11 classes: the instant methods provide such detection.

[0119]A cross-reactive antibodie of the invention may recognize E6 proteins from HPV strains of multiple (e.g., 2, 3, 4, 5, 6, or 7 or more different) classes.

Example 2

Identification of PDZ Domains that Interact with the C-Termini of Oncogenic E6 Proteins

[0120]In order to determine the PDZ domains that can be used to detect oncogenic E6 proteins in a diagnostic assay, the assay was used to identify interactions between E6 PLs and PDZ domains. Peptides were synthesized corresponding to the C-terminal amino acid sequences of E6 proteins from oncogenic strains of human papillomavirus. These peptides were assessed for the ability to bind PDZ domains using an assay and PDZ proteins synthesized from the expression constructs described in greater detail in U.S. patent application Ser. Nos. 09/710,059, 09/724,553 and 09/688,017. Results of these assays that show a high binding affinity are listed in Table 4 below.

[0121]As we can see below, there a large number of PDZ domains that bind some of the oncogenic E6 proteins and the second PDZ domain from MAGI-1 binds all of the oncogenic E6 PLs tested. The PDZ domain of TIP-1 binds all but one of the oncogenic E6 PLs tested, and may be useful in conjunction with MAGI-1 domain 2 for detecting the presence of oncogenic E6 proteins.

[0122]In a similar manner, peptides corresponding to the C-terminal ends of several non-oncogenic E6 proteins were tested with assay. None of the peptides showed any affinity for binding PDZ domains.

TABLE-US-00005 TABLE 4 higher affinity interactions between HPV E6 PLs and PDZ domains HPV PDZ binding partner HPV PDZ binding partner strain (signal 4 and 5 of 0-5) strain (signal 4 and 5 of 0-5) HPV 35 Atrophin-1 interact. prot. HPV 33 Magi1 (PDZ #2) (TEV) (PDZ # 1, 3, 5) (TAL) TIP1 Magi1 (PDZ # 2, 3, 4, 5) DLG1 Lim-Ril Vartul (PDZ #1) FLJ 11215 KIAA 0807 MUPP-1 (PDZ #10) KIAA 1095 (Semcap3) (PDZ KIAA 1095 (PDZ #1) #1) PTN-4 KIAA 1934 (PDZ #1) INADL (PDZ #8) NeDLG (PDZ #1, 2) Vartul (PDZ # 1, 2, 3) Rat outer membrane (PDZ #1) Syntrophin-1 alpha PSD 95 (PDZ #3 and 1-3) Syntrophin gamma-1 TAX IP2 KIAA 0807 KIAA 1634 (PDZ #1) DLG1 (PDZ1, 2) NeDLG (1, 2, 3,) Sim. Rat outer membrane (PDZ #1) MUPP-1 (PDZ #13) PSD 95 (1, 2, 3) HPV 58 Atrophin-1 interact. prot. (PDZ HPV 66 DLG1 (PDZ #1, 2) (TQV) # 1) (STV) NeDLG (PDZ #2) Magi1 (PDZ #2) PSD 95 (PDZ #1, 2, 3) DLG1 (PDZ1, 2) Magi1 (PDZ #2) DLG2 (PDZ #2) KIAA 0807 KIAA 0807 KIAA 1634 (PDZ #1) KIAA 1634 (PDZ #1) DLG2 (PDZ #2) NeDLG (1, 2) Rat outer membrane (PDZ #1) Sim. Rat outer membrane (PDZ NeDLG (1, 2) #1) TIP-1 PSD 95 (1, 2, 3) INADL (PDZ #8) TIP-1 HPV 16* TIP-1 HPV 52 Magi1 (PDZ #2) (TQL) Magi1 (PDZ #2) (TQV) HPV 18* TIP1 (TQV) Magi 1 (PDZ #2) Table 4: Interactions between the E6 C-termini of several HPV variants and human PDZ domains. HPV strain denotes the strain from which the E6 C-terminal peptide sequence information was taken. Peptides used in the assay varied from 18 to 20 amino acids in length, and the terminal four residues are listed in parenthesis. Names to the right of each HPV E6 variant denote the human PDZ domain(s) (with domain number in parenthesis for proteins with multiple PDZ domains) that saturatedbinding with the E6 peptide in assay *denotes that the PDZ domains of hDlgl were not tested against these proteins yet due to limited material, although both have been shown to bind hDlgl in the literature.

[0123]The subject antibodies may be used with these oncogenic HPV E6-binding PDZ proteins in methods of detecting oncogenic strains of HPV.

Materials and Methods for Examples 3-7

[0124]Immunization protocol: Five 8 week-old female BALB/c mice are immunized intraperitoneally, in the footpad, or subcutaneously on day zero with 20 μg of MBP-E6 fusion protein or 100 μg of E6 conjugated-peptide and 20 μg of polyl/polyC polymer or complete Freund's adjuvant. Animals are boosted with 20 μg of E6 protein and polyl/polyC or incomplete Freund's adjuvant. Test bleeds are performed 3 days after the last boostand screened by ELISA against the corresponding E6 protein. Immunoreactive mice have a final boost three days prior to fusion.

[0125]ELISA screening of serum antibody titer and B cell hybridoma supernatants: ELISA plates are coated with appropriate fusion protein, washed, and blocked with PBS containing 2% BSA (Sigma). Then the test sample (immune sera or hybridoma supernatant) is added, along with a pre-immune or irrelevant supernatant negative control. After incubation the plate is washed and anti-mouse IgG-HRP conjugate (Jackson Laboratories) in PBS/2% BSA is added. After thorough washing, TMB substrate is added for 30 minutes, followed by termination of the reaction with 0.18 M H₂SO₄. The plate is then read at 450 nm using a Molecular Devices' THERMO Max microplate reader.

[0126]Fusion: On the day of fusion, the animals are sacrificed, blood collected, and the spleens excised and minced with scissors. The cells are then gently teased up and down with a pipette, filtered through a sterile 70 μm nylon filter and washed by centrifugation. Splenocytes and the FOX-NY myeloma partner (maintained prior to fusion in log growth) are resuspended in serum-free-RPMI medium, combined at a ratio of 4:1 and spun down together. The fusion is then performed by adding 1 ml of 50% PEG (Sigma) drop-wise over one minute, followed by stirring the cells for one minute. Then 2 ml of RPMI/15% FCS media is added drop-wise over two minutes, followed by 8 ml of RPMI/15% FCS over 2 minutes with constant stirring. This mixture is centrifuged, and the cells are gently resuspended at 10⁸ cells/ml in RPMI/15% FCS+1×HAT media (Sigma) and plated out in 96-well flat bottom plates at 200 μl/well. After 5 days ˜100 μl old medium is replaced by aspirating out of wells, and adding 100 μl fresh RPMI/HAT medium. Hybridomas are kept in RPMI/HAT for ˜7 days. Then are grown in RPMI/15% FCS containing 1×HT for ˜1 week. Wells are assayed for antibody activity by ELISA when they are 10-30% confluent.

[0127]Hybridoma cloning, antibody purification and isotyping: Wells whose supernatants give the desired activity were selected for cloning. Cells are cloned by limiting dilution in a 96-well flat bottom plate. Purification of antibodies from tissue culture supernatants is performed by protein G and A affinity chromatography (Amersham). The isotype of the antibodies is determined using Cytometric bead array.

[0128]Cell lines: Cervical cancer cell lines expressing listed strains of HPV E6 were purchased from ATCC, and are shown in the following table:

TABLE-US-00006 ATCC Common E6 GenBank Name Name Organism Tissue type Accession # HTB-31 C-33A human cervix None HTB-32 HT-3 human cervix 30 HTB-33 ME-180 human cervix 68b M73258 HTB-34 MS751 human cervix 45 X74479 HTB-35 SiHa human cervix 16 CRL-1550 CaSki human cervix 16 CRL-1594 C-41 human cervix 18 CRL-1595 C-4-II human cervix 18

[0129]Stably or transiently transfected cells were produced using the following methods:

[0130]The following stable cell lines were made: 3A-HA-E6-26 (expresses HPV 26 E6); C33A-HA-E6-53 (expresses HPV 53 E6); C33A-HA-E6-58 (expresses HPV 58 E6); C33A-HA-E6-59 (expresses HPV 59 E6); C33A-HA-E6-66 (expresses HPV 66 E6); C33A-HA-E6-69 (expresses HPV 69 E6) and C33A-HA-E6-73 (expresses HPV 73 E6).

[0131]Calcium Phosphate Transfection of Mammalian Cell Lines

[0132]Materials: Deionized water, 2M CaCl₂, 2×HBS pH 7.1, 25 mM Chloroquine (1000×), DNA.

[0133]Day 0: Plate 0.8 million cells in each well of a 6-well plate the night before transfection. (2 wells for each construct, therefore, 3 constructs in a 6-well plate)

[0134]Day 1: a) Aliquot appropriate cell media and add Chloroquine (Add 12.5 μl for every 10 ml of media. The extra 2.5 μl is to account for the 500 ul of the calcium phosphate+DNA solution that will be added to the cells later). b) Aspirate media off the cells and add 2 mL of the media+Chloroquine solution. Return cells to incubator. c) In a 5 mL polypropylene tube, add the following in the order listed: i) deionized water, ii) DNA and iii) 2M CaCl₂ as follows:

TABLE-US-00007 DNA Deionized water 2M CaCl2 2X HBS 10 μg (DNA + 64 + dH20 = 500 μl 64 μl 500 μl

[0135]d) Add 500 μl of the DNA mix drop wise to the 2×HBS while bubbling with automatic pipetman and Pasteur pipette; e) Add 500 μl DNA/calcium/phosphate solution to each well; and f) Incubate in incubator for 8 hours, then replace media with normal growth media.

[0136]Day 3: Start selection with G-418 (Gibco) at 1 mg/ml

[0137]Cells for transient expression of HPV 51 E6 were produced by standard methods.

Example 3

HPV-E6 Recombinant Protein Expression and Purification

[0138]Polynucleotides encoding E6 proteins of high-risk HPV types listed above were chemically synthesized (DNA 2.0, Menlo Park, Calif.) or cloned via RT-PCR from cervical cancer cell lines. Both maltose-binding-protein-E6 (MBP-E6) and glutathione-S-transferase-E6 (GST-E6) fusion protein types were used. Production of GST-E6 and MBP-E6 proteins were by standard protocols recommended by the suppliers (Amersham and New England Biolabs, respectively). Proteins were expressed in DH5α E. coli using IPTG driven induction. A 2 h induction at 37° C. yielded GST-E6 or MBP-E6 recombinant proteins at ˜1 mg/L, whereas induction overnight at 20° C. and purification including rebinding of protein to the gel matrix resulted in final yield of 2-10 mg/L. Purity of MBP-E6 proteins was estimated to be >90% based on PAGE analysis. Recombinant E6 fusion proteins were used as immunogens.

Example 4

Immunization, Fusion, Screening and Cloning of Hybridomas Secreting Monoclonal Antibodies Against E6 Protein

[0139]Mice were immunized with each of the HPV E6 proteins. A variety of immunization protocols including varying antigen doses (100 μg-10 μg), adjuvants (CFA/IFA, poly(I)-poly(C), CpG+Alum) and routes (subcutaneous, intraperitoneal) were tested. A service facility for animal care, handling of immunizations and sera collection was contracted (Josman, Napa, Calif.). Immunization projects were set up with 5-15 mice each. Sera of immunized mice were tested in ELISA against the recombinant E6 protein. Mice showing sufficiently high titers (OD above 1 at 1:1000 dilution) against E6 in their sera were selected for fusions.

[0140]To increase the frequency of hybridomas secreting of anti-E6 antibodies, the recombinant E6 protein used in the final boost contained a different tag from that used during the immunization (GST-E6 was used in the boost when immunizations occurred with MBP-E6, and vice versa)

Example 5

Spleen Cells of Selected Mice Were Fused

[0141]Hybridoma supernatants were tested via direct antigen ELISA against the MBP-E6 used in the immunization and MBP protein as negative control. Supernatants that showed reactivity for MBP-E6 (immunogen) but not for MBP were selected for further analysis. Selected supernatants were tested further by slot western blot for reactivity against recombinant MBP-E6 and GST-E6, to reconfirm presence of anti-E6 mAb. At this stage, hybridomas were cloned by limiting dilution to isolate hybridoma clones secreting anti-E6 mAb.

[0142]To further characterize the reactivity of the hybridomas, selected supernatants were tested in an ELISA against the recombinant E6 proteins, as well as GST-INADL (PDZ) and GST-MAGI1-PDZ1 that served as negative controls. GST-INADL represents a class of proteins that, when purified in prokaryotic expression systems, tend to be associated with a bacterial contaminating that are also present in the MBP-/GST-E6 protein preparations used for immunizations. This control ensured that reactivity found in supernatants reflected a mAb binding to HPV-E6, and not against the associated contaminants.

Example 6

Cross-Reactivity Pattern of Anti-E6 Monoclonal Antibodies

[0143]The cross-reactivity pattern of anti-E6 mAbs against E6 proteins other than the one used as immunogen was tested. For this E6 panel test, a direct ELISA approach is used (recombinant E6 protein is coated on the plate).

[0144]Monoclonal antibodies against the E6 protein of high-risk HPV types that cause cervical cancer (e.g., HPV 16, 18, 26, 30, 31, 34, 45, 51, 52, 53, 58, 59, 66, 68b, 69, 70, 73, 82) were produced.

[0145]A summary of results showing cross-reactivity of the antibodies produced is shown In Table 5 below.

TABLE-US-00008 TABLE 5 HPV-E6 HPV-E6 type binding binding Endogenous E6 mAb profile-direct profile S2 detection S2 Immunogen and Immunization route designation ELISA ELISA ELISA boosts/last boost and adjuvant F12-1B9 18, 45, 66 N.D. N.D. HPV18-[MBP]-E6/ subcutaneous/Adjuvant: F12-1C9 18 N.D. N.D. HPV18-[GST]-E6 complete/incomplete F12-1H12 18 N.D. N.D. Freund's (initial/ F12-2D2 18, 45, 66 N.D. N.D. follow up injections) F12-3B2 18 N.D. N.D. F12-3D5 18, 45, 66, 82 18, 45 18, 45 F12-4A11 18 18 18 F12-4 E2 18 18, 45 N.D. F12-5C2 18 N.D. N.D. F12-6D9 18, 45 N.D. N.D. F12-6F5 18 N.D. N.D. F12-6F6 18, 45 N.D. N.D. F12-6H2 18, 45, 66, 82 N.D. N.D. F12-7A10 18, 45 N.D. N.D. F12-7F10 18 N.D. N.D. F12-8A3 18, 45 N.D. N.D. F12-8B8 18 N.D. N.D. F16-4H12 16, 35 16 N.D. HPV16-[MBP]-E6/ subcutaneous/Adjuvant: F16-5D5 16, 35 16 does not HPV16-[GST]-E6 complete/incomplete recognize 16 HPV58-[MBP]-E6/ Freund's (initial/ follow up injections) F17-1 E11 26, 51, 52, 53, 58 N.D. N.D. subctaneous/Adjuvant: F17-6G9 33, 58 58 does not HPV58-[GST]-E6 complete/incomplete recognize 58 Freund's (initial/ follow up injections) F18-3G11 16 16 does not HPV16-[GST]-E6/ subcutaneous/Adjuvant: recognize 16 HPV16-[MBP]-E6 complete/incomplete F18-4C9 16 N.D. N.D. Freund's (initial/ F18-5H3 16 N.D. N.D. follow up injections) F18-7H8 16 N.D. N.D. F18-8G11 16 N.D. N.D. F18-9B10 16, 73 N.D. N.D. F18-10 E6 16 16 16 F18-10 E10 16 N.D. N.D. F19-6D10 18, 68b 18, 68b does not DNA plasmid recognize 18 or immunization; boost 68b with HPV18-E6 (MBP- F19-6F9 18, 68b 18, 68b N.D. E6/GST-E6) F19-7B12 18, 35, 68b N.D. N.D. F19-7C7 18, 68b N.D. N.D. F19-8E2 18, 35, 68b N.D. N.D. F20-2H5 16, 18, 35, 45 18, 35, 45 does not HPV45-[MBP]-E6/ subcutaneous/Adjuvant: recognize 18 or HPV45-[GST]-E6 complete/incomplete 45; 35 N.D. Freund's (initial/ follow up injections) F21-1D12 18, 30, 52, 58 30, 58 does not HPV58-[MBP]-E6/ footpad injection/ recognize 30 or HPV58-[GST]-E6 Adjuvant: CpG-ALUM 58 F21-3A3 18, 58 N.D. N.D. F21-3H2 18, 30, 52, 58 58 N.D. F21-4 E10 18, 30, 52, 58 58 N.D. F21-4F9 18, 33, 58 N.D. N.D. F21-4H1 18, 30, 33, 52, 33, 58 33, 58 58 F21-5B2 16, 18, 30, 52, N.D. N.D. 58, 59, 68b F22-1C12 26, 51, 69 51 51 HPV51-[MBP]-E6/ subctaneous/Adjuvant: F22-10D11 26, 30, N.D. N.D. HPV51-[GST]-E6 complete/incomplete 31, 35, 51, 53, Freund's (initial/ 66, 69, 82 follow up injections) F22-10F10 26, 51, 69 51 N.D. F24-2D6 26, 51, 69, 82 26, 69 26, 69 HPV69-[MBP]-E6/ subcutaneous/Adjuvant: F24-4B12 26, 51, 53, 69, N.D. N.D. HPV69-[GST]-E6 complete/incomplete 73, 82 Freund's (initial/ F24-4F2 26, 51, 69, 82 26, 69, 82 26, 69; 82 N.D. follow up injections) F24-4G1 26, 51, 69, 82 N.D. N.D. F24-8H12 26, 51, 69, 82 26, 69, 82 N.D. F24-9H12 26, 51, 69, 82 26, 69 N.D. F25-2D11 73 N.D. N.D. HPV73-[MBP]-E6/ subcutaneous/Adjuvant: F25-3D10 53, 73, 82 N.D. N.D. HPV73-[GST]-E6 complete/incomplete F25-3 E5 16, 34, 59, 70, N.D. N.D. Freund's (initial/ 73 follow up injections) F25-4C11 16, 34, 59, 70, 34 does not 73 recognize 73, 34 N.D. F26-1B10 51, 53 N.D. N.D. HPV53-[MBP]-E6/ subcutaneous/Adjuvant: F26-1B11 53 N.D. N.D. HPV53-[GST]-E6 complete/incomplete F26-1D9 53 N.D. N.D. Freund's (initial/ F26-1D11 53 N.D. N.D. follow up injections) F26-2B12 53 N.D. N.D. F26-2G5 53 N.D. N.D. F26-3A8 30, 53, 66 N.D. N.D. F26-5H5 53 N.D. N.D. F26-6D10 53 N.D. N.D. F26-8B7 53 N.D. N.D. F26-8H9 53 N.D. N.D. F26-9C2 53 N.D. N.D. F26-9C7 53 N.D. N.D. F26-9D8 53 N.D. N.D. F26-9G5 53, 73, 82 N.D. N.D. F27-3A4 59 N.D. N.D. HPV59-[MBP]-E6/ subcutaneous/Adjuvant: HPV59-[GST]-E6 complete/incomplete Freund's (initial/ follow up injections) 6F4 16 16, 35, 69 recognizes 16 HP VI 6- poly-I/ and 69, 35 N.D. [GST]E6/HPV16- poly-C adjuvant/ [GST]E6 three immunizations 4C6 16 16 N.D. HPV16- poly-I/ [GST]E6/HPV16- poly-C adjuvant/ [GST]E6 three immunizations 3F8 16 16, 35, 51, N.D. HPV16-[MBP]E6-C- poly-I/ 82, 31, 33 terminal poly-C adjuvant/ and 58 portion/HPV16- three immunizations [MBP]E6-C-terminal portion

[0146]FIG. 3 shows results obtained from a slot western blot of recombinant E6 protein, probed with hybridoma supernatants.

Example 7

Selection of Antibodies for HPV Diagnostic Test

[0147]Supernatants from hybridomas reacting with E6 proteins are tested together with the oncogenic PL detector in a sandwich ELISA with recombinant E6 fusion protein.

[0148]Monoclonal antibodies are tested in HPV diagnostic ELISA for their ability to detect E6 from cervical cancer cell lines or cells transfected with E6 (if cell lines are unavailable).

[0149]It is evident from the above results and discussion that the subject invention provides an important new means for detecting HPV E6 proteins. In particular, the subject invention provides a system for detecting oncogenic strains of HPV. It is superior to current methods because the PDZ protein isolates the oncogenic E6 protein from other analytes of a complex biological sample, and the protein is detected using an antibody that cross-reacts with more than one E6 protein. The specificity of detection lies in the PDZ protein and the antibody does not need to bind only oncogenic E6 proteins, as currently required in conventional methods. Accordingly, the subject methods and systems find use in a variety of different diagnostic applications. Accordingly, the present invention represents a significant contribution to the art.

Sequence CWU 1

366125PRTHuman papillomavirus 1Phe Gln Asp Pro Gln Glu Arg Pro Arg Lys Leu Pro Gln Leu Cys Thr1 5 10 15Glu Leu Gln Thr Thr Ile His Asp Ile 20 25225PRTHuman papillomavirus 2Phe Glu Asp Pro Thr Arg Arg Pro Tyr Lys Leu Pro Asp Leu Cys Thr1 5 10 15Glu Leu Asn Thr Ser Leu Gln Asp Ile 20 25323PRTHuman papillomavirus 3Leu Leu Ile Arg Cys Ile Asn Cys Gln Lys Pro Leu Cys Pro Glu Glu1 5 10 15Lys Gln Arg His Leu Asp Lys 20423PRTHuman papillomavirus 4Leu Leu Ile Arg Cys Leu Arg Cys Gln Lys Pro Leu Asn Pro Ala Glu1 5 10 15Lys Leu Arg His Leu Asn Glu 20524PRTHuman papillomavirus 5Arg His Leu Asp Lys Lys Gln Arg Phe His Asn Ile Arg Gly Arg Trp1 5 10 15Thr Gly Arg Cys Met Ser Cys Cys 20624PRTHuman papillomavirus 6Arg His Leu Asn Glu Lys Arg Arg Phe His Asn Ile Ala Gly His Tyr1 5 10 15Arg Gly Gln Cys His Ser Cys Cys 20712PRTHuman papillomavirus 7Arg Pro Arg Lys Leu Pro Gln Leu Cys Thr Glu Leu1 5 10812PRTHuman papillomavirus 8Arg Pro Tyr Lys Leu Pro Asp Leu Cys Thr Glu Leu1 5 10912PRTHuman papillomavirus 9Leu Leu Ile Arg Cys Ile Asn Cys Gln Lys Pro Leu1 5 101012PRTHuman papillomavirus 10Leu Leu Ile Arg Cys Leu Arg Cys Gln Lys Pro Leu1 5 101112PRTHuman papillomavirus 11Arg His Leu Asp Lys Lys Gln Arg Phe His Asn Ile1 5 101212PRTHuman papillomavirus 12Arg His Leu Asn Glu Lys Arg Arg Phe His Asn Ile1 5 1013158PRTHuman papillomavirus 13Met His Gln Lys Arg Thr Ala Met Phe Gln Asp Pro Gln Glu Arg Pro1 5 10 15Arg Lys Leu Pro Gln Leu Cys Thr Glu Leu Gln Thr Thr Ile His Asp 20 25 30Ile Ile Leu Glu Cys Val Tyr Cys Lys Gln Gln Leu Leu Arg Arg Glu 35 40 45Val Tyr Asp Phe Ala Phe Arg Asp Leu Cys Ile Val Tyr Arg Asp Gly 50 55 60Asn Pro Tyr Ala Val Cys Asp Lys Cys Leu Lys Phe Tyr Ser Lys Ile65 70 75 80Ser Glu Tyr Arg His Tyr Cys Tyr Ser Leu Tyr Gly Thr Thr Leu Glu 85 90 95Gln Gln Tyr Asn Lys Pro Leu Cys Asp Leu Leu Ile Arg Cys Ile Asn 100 105 110Cys Gln Lys Pro Leu Cys Pro Glu Glu Lys Gln Arg His Leu Asp Lys 115 120 125Lys Gln Arg Phe His Asn Ile Arg Gly Arg Trp Thr Gly Arg Cys Met 130 135 140Ser Cys Cys Arg Ser Ser Arg Thr Arg Arg Glu Thr Gln Leu145 150 15514149PRTHuman papillomavirus 14Met Phe Gln Asp Pro Ala Glu Arg Pro Tyr Lys Leu His Asp Leu Cys1 5 10 15Asn Glu Val Glu Glu Ser Ile His Glu Ile Cys Leu Asn Cys Val Tyr 20 25 30Cys Lys Gln Glu Leu Gln Arg Ser Glu Val Tyr Asp Phe Ala Cys Tyr 35 40 45Asp Leu Cys Ile Val Tyr Arg Glu Gly Gln Pro Tyr Gly Val Cys Met 50 55 60Lys Cys Leu Lys Phe Tyr Ser Lys Ile Ser Glu Tyr Arg Trp Tyr Arg65 70 75 80Tyr Ser Val Tyr Gly Glu Thr Leu Glu Lys Gln Cys Asn Lys Gln Leu 85 90 95Cys His Leu Leu Ile Arg Cys Ile Thr Cys Gln Lys Pro Leu Cys Pro 100 105 110Val Glu Lys Gln Arg His Leu Glu Glu Lys Lys Arg Phe His Asn Ile 115 120 125Gly Gly Arg Trp Thr Gly Arg Cys Met Ser Cys Trp Lys Pro Thr Arg 130 135 140Arg Glu Thr Glu Val14515149PRTHuman papillomavirus 15Met Phe Gln Asp Ala Glu Glu Lys Pro Arg Thr Leu His Asp Leu Cys1 5 10 15Gln Ala Leu Glu Thr Ser Val His Glu Ile Glu Leu Lys Cys Val Glu 20 25 30Cys Lys Lys Thr Leu Gln Arg Ser Glu Val Tyr Asp Phe Val Phe Ala 35 40 45Asp Leu Arg Ile Val Tyr Arg Asp Gly Asn Pro Phe Ala Val Cys Lys 50 55 60Val Cys Leu Arg Leu Leu Ser Lys Ile Ser Glu Tyr Arg His Tyr Asn65 70 75 80Tyr Ser Leu Tyr Gly Asp Thr Leu Glu Gln Thr Leu Lys Lys Cys Leu 85 90 95Asn Glu Ile Leu Ile Arg Cys Ile Ile Cys Gln Arg Pro Leu Cys Pro 100 105 110Gln Glu Lys Lys Arg His Val Asp Leu Asn Lys Arg Phe His Asn Ile 115 120 125Ser Gly Arg Trp Thr Gly Arg Cys Ala Val Cys Trp Arg Pro Arg Arg 130 135 140Arg Gln Thr Gln Val14516149PRTHuman papillomavirus 16Met Phe Gln Asp Thr Glu Glu Lys Pro Arg Thr Leu His Asp Leu Cys1 5 10 15Gln Ala Leu Glu Thr Thr Ile His Asn Ile Glu Leu Gln Cys Val Glu 20 25 30Cys Lys Lys Pro Leu Gln Arg Ser Glu Val Tyr Asp Phe Ala Phe Ala 35 40 45Asp Leu Thr Val Val Tyr Arg Glu Gly Asn Pro Phe Gly Ile Cys Lys 50 55 60Leu Cys Leu Arg Phe Leu Ser Lys Ile Ser Glu Tyr Arg His Tyr Asn65 70 75 80Tyr Ser Val Tyr Gly Asn Thr Leu Glu Gln Thr Val Lys Lys Pro Leu 85 90 95Asn Glu Ile Leu Ile Arg Cys Ile Ile Cys Gln Arg Pro Leu Cys Pro 100 105 110Gln Glu Lys Lys Arg His Val Asp Leu Asn Lys Arg Phe His Asn Ile 115 120 125Ser Gly Arg Trp Ala Gly Arg Cys Ala Ala Cys Trp Arg Ser Arg Arg 130 135 140Arg Glu Thr Ala Leu14517148PRTHuman papillomavirus 17Met Phe Glu Asp Pro Ala Thr Arg Pro Arg Thr Leu His Glu Leu Cys1 5 10 15Glu Val Leu Glu Glu Ser Val His Glu Ile Arg Leu Gln Cys Val Gln 20 25 30Cys Lys Lys Glu Leu Gln Arg Arg Glu Val Tyr Lys Phe Leu Phe Thr 35 40 45Asp Leu Arg Ile Val Tyr Arg Asp Asn Asn Pro Tyr Gly Val Cys Ile 50 55 60Met Cys Leu Arg Phe Leu Ser Lys Ile Ser Glu Tyr Arg His Tyr Gln65 70 75 80Tyr Ser Leu Tyr Gly Lys Thr Leu Glu Glu Arg Val Lys Lys Pro Leu 85 90 95Ser Glu Ile Thr Ile Arg Cys Ile Ile Cys Gln Thr Pro Leu Cys Pro 100 105 110Glu Glu Lys Glu Arg His Val Asn Ala Asn Lys Arg Phe His Asn Ile 115 120 125Met Gly Arg Trp Thr Gly Arg Cys Ser Glu Cys Trp Arg Pro Arg Pro 130 135 140Val Thr Gln Val14518149PRTHuman papillomavirus 18Met Phe Lys Asn Pro Ala Glu Arg Pro Arg Lys Leu His Glu Leu Ser1 5 10 15Ser Ala Leu Glu Ile Pro Tyr Asp Glu Leu Arg Leu Asn Cys Val Tyr 20 25 30Cys Lys Gly Gln Leu Thr Glu Thr Glu Val Leu Asp Phe Ala Phe Thr 35 40 45Asp Leu Thr Ile Val Tyr Arg Asp Asp Thr Pro His Gly Val Cys Thr 50 55 60Lys Cys Leu Arg Phe Tyr Ser Lys Val Ser Glu Phe Arg Trp Tyr Arg65 70 75 80Tyr Ser Val Tyr Gly Thr Thr Leu Glu Lys Leu Thr Asn Lys Gly Ile 85 90 95Cys Asp Leu Leu Ile Arg Cys Ile Thr Cys Gln Arg Pro Leu Cys Pro 100 105 110Glu Glu Lys Gln Arg His Leu Asp Lys Lys Lys Arg Phe His Asn Ile 115 120 125Gly Gly Arg Trp Thr Gly Arg Cys Ile Ala Cys Trp Arg Arg Pro Arg 130 135 140Thr Glu Thr Gln Val14519148PRTHuman papillomavirus 19Met Leu Phe Pro Asn Ser Glu Glu Arg Pro Tyr Lys Leu Gln Ala Leu1 5 10 15Cys Asp Glu Val Asn Ile Ser Ile His Asp Ile Asn Leu Asp Cys Val 20 25 30Phe Cys Gln Arg Gly Leu Tyr Arg Ser Glu Val Tyr Asp Phe Ala Phe 35 40 45Ser Asp Leu Cys Ile Val Tyr Arg Lys Asp Lys Pro Tyr Gly Val Cys 50 55 60Gln Pro Cys Leu Lys Phe Tyr Ser Lys Ile Arg Glu Tyr Arg Arg Tyr65 70 75 80Arg Gln Ser Val Tyr Gly Thr Thr Leu Glu Asn Leu Thr Asn Lys Gln 85 90 95Leu Cys Asn Ile Leu Ile Arg Cys Gly Lys Cys Gln Lys Pro Leu Cys 100 105 110Pro Leu Glu Lys Gln Lys His Val Asp Glu Lys Lys Arg Phe His Gln 115 120 125Ile Ala Glu Gln Trp Thr Gly Arg Cys Thr Arg Cys Trp Arg Pro Ser 130 135 140Ala Thr Val Val14520153PRTHuman papillomavirus 20Met Ala Phe Lys Phe Glu Asn Thr Gly Glu Arg Pro Arg Thr Val His1 5 10 15His Leu Cys Glu Val Gln Glu Thr Ser Leu Leu Glu Leu Gln Leu Gln 20 25 30Cys Val Tyr Cys Lys Lys Glu Leu Ser Ser Ser Glu Val Tyr Asn Phe 35 40 45Ala Cys Lys Asp Leu Arg Leu Val Tyr Arg Glu Asp Ser Pro Tyr Ala 50 55 60Val Cys Asn Phe Cys Leu Leu Phe Tyr Ser Lys Val Arg Lys Ile Arg65 70 75 80His Tyr Asn Tyr Ser Leu Tyr Gly Ala Ser Leu Val Ala Leu Thr Lys 85 90 95Lys Glu Leu Phe Asp Leu Leu Ile Arg Cys Tyr Arg Cys Gln Gln Pro 100 105 110Leu Thr Pro Glu Glu Lys Gln Leu His Cys Glu Tyr Lys Lys Arg Phe 115 120 125His Arg Ile Ser Arg Thr Trp Thr Gly Leu Cys Leu Gln Cys Trp Arg 130 135 140His Thr Thr Ser Thr Glu Thr Ala Val145 15021154PRTHuman papillomavirus 21Met Asp Arg Gln Leu Phe Glu Asn Thr Glu Glu Arg Pro Arg Thr Leu1 5 10 15His Gln Leu Cys Glu Val Val Asn Lys Pro Leu Leu Glu Leu Gln Leu 20 25 30Gly Cys Val Phe Cys Lys Lys Ala Leu Thr Ala Ser Glu Val Tyr Asn 35 40 45Phe Ala Tyr Thr Asp Leu Arg Val Val Tyr Arg Asp Gly Tyr Pro Tyr 50 55 60Gly Val Cys Lys Phe Cys Leu Leu Phe Tyr Ser Lys Val Arg Lys Leu65 70 75 80Arg Tyr Tyr Asn Cys Ser Val Tyr Gly Ala Ser Leu Glu Ala Leu Thr 85 90 95Lys Lys Lys Leu Ser Asp Leu Ser Ile Arg Cys Tyr Arg Cys Gln His 100 105 110Pro Leu Thr Pro Glu Glu Lys Gln Leu His Cys Asp Tyr Lys Lys Arg 115 120 125Phe His Lys Ile Ser His Met Trp Thr Gly Ser Cys Leu Thr Cys Trp 130 135 140Arg His Thr Thr Ala Thr Glu Ser Ala Val145 15022155PRTHuman papillomavirus 22Met Glu Pro Gln Phe Asn Asn Pro Gln Glu Arg Pro Arg Ser Leu His1 5 10 15His Leu Ser Glu Val Leu Glu Ile Pro Leu Ile Asp Leu Arg Leu Ser 20 25 30Cys Val Tyr Cys Lys Lys Glu Leu Thr Arg Ala Glu Val Tyr Asn Phe 35 40 45Ala Cys Thr Glu Leu Lys Leu Val Tyr Arg Asp Asp Phe Pro Tyr Ala 50 55 60Val Cys Arg Val Cys Leu Leu Phe Tyr Ser Lys Val Arg Lys Tyr Arg65 70 75 80Tyr Tyr Asp Tyr Ser Val Tyr Gly Ala Thr Leu Glu Ser Ile Thr Lys 85 90 95Lys Gln Leu Cys Asp Leu Leu Ile Arg Cys Tyr Arg Cys Gln Ser Pro 100 105 110Leu Thr Pro Glu Glu Lys Gln Leu His Cys Asp Arg Lys Arg Arg Phe 115 120 125His Leu Ile Ala His Gly Trp Thr Gly Ser Cys Leu Gly Cys Trp Arg 130 135 140Gln Thr Ser Arg Glu Pro Arg Glu Ser Thr Val145 150 15523155PRTHuman papillomavirus 23Met Asp Ser Ile Phe Ser Asn Thr Gln Glu Arg Pro Arg Ser Leu His1 5 10 15His Leu Ser Glu Val Leu Gln Ile Pro Leu Leu Asp Leu Arg Leu Ser 20 25 30Cys Val Tyr Cys Lys Lys Glu Leu Thr Ser Leu Glu Leu Tyr Arg Phe 35 40 45Ala Cys Ile Glu Leu Lys Leu Val Tyr Arg Asn Asn Trp Pro Tyr Ala 50 55 60Val Cys Arg Val Cys Leu Leu Phe Tyr Ser Lys Val Arg Lys Tyr Arg65 70 75 80Tyr Tyr Lys Tyr Ser Val Tyr Gly Ala Thr Leu Glu Ser Ile Thr Lys 85 90 95Lys Gln Leu Ser Asp Leu Ser Ile Arg Cys Tyr Arg Cys Gln Cys Pro 100 105 110Leu Thr Pro Glu Glu Lys Gln Leu His Cys Glu His Lys Arg Arg Phe 115 120 125His Tyr Ile Ala Tyr Ala Trp Thr Gly Ser Cys Leu Gln Cys Trp Arg 130 135 140His Thr Ser Arg Gln Ala Thr Glu Ser Thr Val145 150 15524151PRTHuman papillomavirus 24Met Phe Glu Asp Lys Arg Glu Arg Pro Arg Thr Leu His Glu Leu Cys1 5 10 15Glu Ala Leu Asn Val Ser Met His Asn Ile Gln Val Val Cys Val Tyr 20 25 30Cys Lys Lys Glu Leu Cys Arg Ala Asp Val Tyr Asn Val Ala Phe Thr 35 40 45Glu Ile Lys Ile Val Tyr Arg Asp Asn Asn Pro Tyr Ala Val Cys Lys 50 55 60Gln Cys Leu Leu Phe Tyr Ser Lys Ile Arg Glu Tyr Arg Arg Tyr Ser65 70 75 80Arg Ser Val Tyr Gly Thr Thr Leu Glu Ala Ile Thr Lys Lys Ser Leu 85 90 95Tyr Asp Leu Ser Ile Arg Cys His Arg Cys Gln Arg Pro Leu Gly Pro 100 105 110Glu Glu Lys Gln Lys Leu Val Asp Glu Lys Lys Arg Phe His Glu Ile 115 120 125Ala Gly Arg Trp Thr Gly Gln Cys Ala Asn Cys Trp Gln Arg Thr Arg 130 135 140Gln Arg Asn Glu Thr Gln Val145 15025151PRTHuman papillomavirus 25Met Phe Glu Asp Ile Arg Glu Arg Pro Arg Thr Leu His Glu Leu Cys1 5 10 15Glu Ala Cys Asn Thr Ser Met His Asn Ile Gln Val Leu Cys Val Tyr 20 25 30Cys Lys Lys Glu Leu Cys Arg Ala Asp Val Tyr Asn Val Ala Phe Thr 35 40 45Glu Leu Arg Ile Val Tyr Arg Asp Asn Thr Pro Tyr Ala Ala Cys Lys 50 55 60Lys Cys Leu Met Phe Tyr Ser Arg Ile Arg Glu Tyr Arg Arg Tyr Ser65 70 75 80Arg Ser Val Tyr Gly Ala Thr Leu Glu Ala Ile Thr Asn Lys Ser Leu 85 90 95Tyr Glu Leu Leu Ile Arg Cys His Arg Cys Gln Arg Pro Leu Gly Pro 100 105 110Glu Glu Lys Gln Lys Val Val Asp Asp Lys Lys Arg Phe His Glu Ile 115 120 125Ala Gly Arg Trp Thr Gly Gln Cys Ala Asn Cys Arg Lys Pro Pro Arg 130 135 140Gln Arg Ser Glu Thr Gln Val145 15026151PRTHuman papillomavirus 26Met Phe Gln Asp Pro Arg Glu Arg Pro Arg Thr Ile His Glu Leu Cys1 5 10 15Glu Ala Leu Asn Thr Pro Leu Gln Ser Leu Gln Val Gln Cys Val Tyr 20 25 30Cys Lys Lys Thr Leu Glu Trp Ala Asp Val Tyr Asn Phe Ala Ile Cys 35 40 45Asp Leu Arg Ile Val Tyr Arg Asn Asp Ser Ala Tyr Gly Ala Cys Lys 50 55 60Lys Cys Ile Ile Phe Tyr Ser Lys Ile Ile Glu Tyr Arg Arg Tyr Thr65 70 75 80Ser Ser Val Tyr Gly Ala Thr Leu Glu Ala Arg Pro Lys Arg Ser Leu 85 90 95Cys Asn Leu Leu Ile Arg Cys His Arg Cys Gln Ile Pro Leu Gly Pro 100 105 110Glu Glu Lys Gln Arg Ile Val Asp Glu Lys Arg Arg Phe His Glu Ile 115 120 125Ala Gly Tyr Trp Lys Gly Leu Cys Thr Asn Cys Trp Arg Pro Arg Arg 130 135 140Glu Ala Thr Glu Thr Gln Val145 15027150PRTHuman papillomavirus 27Met Phe Glu Asp Pro Arg Glu Arg Pro Arg Thr Leu His Glu Leu Cys1 5 10 15Glu Ser Leu Asn Thr Thr Leu Gln Asn Leu Gln Val Gln Cys Val Tyr 20 25 30Cys Lys Glu Thr Leu Gln Trp Ala Asp Val Tyr Asn Phe Ala Ile Cys 35 40 45Asp Leu Arg Val Val Tyr Arg Asp Arg Ser Pro Tyr Ala Ala Cys Lys 50 55 60Arg Cys Val Ile Phe Tyr Ser Lys Ile Thr Glu Tyr Arg Arg Tyr Thr65

70 75 80Cys Ser Val Tyr Gly Ala Thr Leu Glu Ala Leu Thr Lys Lys Ser Leu 85 90 95Cys Asn Leu Leu Ile Arg Cys His Arg Cys Gln Met Pro Leu Gly Pro 100 105 110Glu Glu Lys Gln Arg Ile Val Asp Glu Lys Arg Arg Phe His Glu Ile 115 120 125Ala Gly Gln Trp Lys Gly Leu Cys Thr Asn Cys Trp Arg Pro Arg Arg 130 135 140Gln Thr Glu Thr Gln Val145 15028158PRTHuman papillomavirus 28Met Ala Arg Phe Glu Asp Pro Thr Arg Arg Pro Tyr Lys Leu Pro Asp1 5 10 15Leu Cys Thr Glu Leu Asn Thr Ser Leu Gln Asp Ile Glu Ile Thr Cys 20 25 30Val Tyr Cys Lys Thr Val Leu Glu Leu Thr Glu Val Phe Glu Phe Ala 35 40 45Phe Lys Asp Leu Phe Val Val Tyr Arg Asp Ser Ile Pro His Ala Ala 50 55 60Cys His Lys Cys Ile Asp Phe Tyr Ser Arg Ile Arg Glu Leu Arg His65 70 75 80Tyr Ser Asp Ser Val Tyr Gly Asp Thr Leu Glu Lys Leu Thr Asn Thr 85 90 95Gly Leu Tyr Asn Leu Leu Ile Arg Cys Leu Arg Cys Gln Lys Pro Leu 100 105 110Asn Pro Ala Glu Lys Leu Arg His Leu Asn Glu Lys Arg Arg Phe His 115 120 125Asn Ile Ala Gly His Tyr Arg Gly Gln Cys His Ser Cys Cys Asn Arg 130 135 140Ala Arg Gln Glu Arg Leu Gln Arg Arg Arg Glu Thr Gln Val145 150 15529158PRTHuman papillomavirus 29Met Ala Arg Phe Asp Asp Pro Lys Gln Arg Pro Tyr Lys Leu Pro Asp1 5 10 15Leu Cys Thr Glu Leu Asn Thr Ser Leu Gln Asp Val Ser Ile Ala Cys 20 25 30Val Tyr Cys Lys Ala Thr Leu Glu Arg Thr Glu Val Tyr Gln Phe Ala 35 40 45Phe Lys Asp Leu Cys Ile Val Tyr Arg Asp Cys Ile Ala Tyr Ala Ala 50 55 60Cys His Lys Cys Ile Asp Phe Tyr Ser Arg Ile Arg Glu Leu Arg Tyr65 70 75 80Tyr Ser Asn Ser Val Tyr Gly Glu Thr Leu Glu Lys Ile Thr Asn Thr 85 90 95Glu Leu Tyr Asn Leu Leu Ile Arg Cys Leu Arg Cys Gln Lys Pro Leu 100 105 110Asn Pro Ala Glu Lys Arg Arg His Leu Lys Asp Lys Arg Arg Phe His 115 120 125Ser Ile Ala Gly Gln Tyr Arg Gly Gln Cys Asn Thr Cys Cys Asp Gln 130 135 140Ala Arg Gln Glu Arg Leu Arg Arg Arg Arg Glu Thr Gln Val145 150 15530158PRTHuman papillomavirus 30Met Ala Arg Phe His Asn Pro Ala Glu Arg Pro Tyr Lys Leu Pro Asp1 5 10 15Leu Cys Thr Thr Leu Asp Thr Thr Leu Gln Asp Ile Thr Ile Ala Cys 20 25 30Val Tyr Cys Arg Arg Pro Leu Gln Gln Thr Glu Val Tyr Glu Phe Ala 35 40 45Phe Ser Asp Leu Tyr Val Val Tyr Arg Asp Gly Glu Pro Leu Ala Ala 50 55 60Cys Gln Ser Cys Ile Lys Phe Tyr Ala Lys Ile Arg Glu Leu Arg Tyr65 70 75 80Tyr Ser Asp Ser Val Tyr Ala Thr Thr Leu Glu Asn Ile Thr Asn Thr 85 90 95Lys Leu Tyr Asn Leu Leu Ile Arg Cys Met Cys Cys Leu Lys Pro Leu 100 105 110Cys Pro Ala Glu Lys Leu Arg His Leu Asn Ser Lys Arg Arg Phe His 115 120 125Lys Ile Ala Gly Ser Tyr Thr Gly Gln Cys Arg Arg Cys Trp Thr Thr 130 135 140Lys Arg Glu Asp Arg Arg Leu Thr Arg Arg Glu Thr Gln Val145 150 15531162PRTHuman papillomavirus 31Met Ser Ile Pro Met Ala Leu Phe His Asn Pro Glu Glu Arg Pro Tyr1 5 10 15Lys Leu Pro Asp Leu Cys Arg Thr Leu Asp Thr Thr Leu His Asp Val 20 25 30Thr Ile Asp Cys Val Tyr Cys Arg Arg Gln Leu Gln Arg Thr Glu Val 35 40 45Tyr Glu Phe Ala Phe Gly Asp Leu Asn Val Val Tyr Arg Asp Gly Val 50 55 60Pro Leu Ala Ala Cys Gln Ser Cys Ile Lys Phe Tyr Ala Lys Ile Arg65 70 75 80Glu Leu Arg Tyr Tyr Ser Glu Ser Val Tyr Ala Thr Thr Leu Glu Thr 85 90 95Ile Thr Asn Thr Lys Leu Tyr Asp Leu Ser Ile Arg Cys Met Cys Cys 100 105 110Leu Lys Pro Leu Ser Pro Ala Glu Lys Leu Arg His Leu Asn Ser Lys 115 120 125Arg Arg Phe His Lys Ile Ala Gly Asn Phe Thr Gly Gln Cys Arg His 130 135 140Cys Trp Thr Ser Lys Arg Glu Asp Arg Arg Arg Thr Arg Gln Glu Thr145 150 155 160Gln Val32160PRTHuman papillomavirus 32Met Ala Arg Phe Glu Asp Pro Thr Gln Arg Pro Tyr Lys Leu Pro Asp1 5 10 15Leu Ser Thr Thr Leu Asn Ile Pro Leu His Asp Ile Arg Ile Asn Cys 20 25 30Val Phe Cys Lys Gly Glu Leu Gln Glu Arg Glu Val Phe Glu Phe Ala 35 40 45Phe Asn Asp Leu Phe Ile Val Tyr Arg Asp Cys Thr Pro Tyr Ala Ala 50 55 60Cys Leu Lys Cys Ile Ser Phe Tyr Ala Arg Val Arg Glu Leu Arg Tyr65 70 75 80Tyr Arg Asp Ser Val Tyr Gly Glu Thr Leu Glu Ala Glu Thr Lys Thr 85 90 95Pro Leu His Glu Leu Leu Ile Arg Cys Tyr Arg Cys Leu Lys Pro Leu 100 105 110Cys Pro Thr Asp Lys Leu Lys His Ile Thr Glu Lys Arg Arg Phe His 115 120 125Asn Ile Ala Gly Ile Tyr Thr Gly Gln Cys Arg Gly Cys Arg Thr Arg 130 135 140Ala Arg His Leu Arg Gln Gln Arg Gln Ala Arg Ser Glu Thr Leu Val145 150 155 1603310PRTHuman papillomavirus 33Gly Tyr Cys Arg Asn Cys Ile Arg Lys Gln1 5 103410PRTHuman papillomavirus 34Trp Thr Thr Cys Met Glu Asp Leu Leu Pro1 5 103510PRTHuman papillomavirus 35Gly Ile Cys Arg Leu Cys Lys His Phe Gln1 5 103610PRTHuman papillomavirus 36Lys Gly Leu Cys Arg Gln Cys Lys Gln Ile1 5 103710PRTHuman papillomavirus 37Trp Leu Arg Cys Thr Val Arg Ile Pro Gln1 5 103810PRTHuman papillomavirus 38Arg Gln Cys Lys His Phe Tyr Asn Asp Trp1 5 103910PRTHuman papillomavirus 39Cys Arg Asn Cys Ile Ser His Glu Gly Arg1 5 104010PRTHuman papillomavirus 40Cys Cys Arg Asn Cys Tyr Glu His Glu Gly1 5 104110PRTHuman papillomavirus 41Ser Ser Arg Thr Arg Arg Glu Thr Gln Leu1 5 104210PRTHuman papillomavirus 42Arg Leu Gln Arg Arg Arg Glu Thr Gln Val1 5 104310PRTHuman papillomavirus 43Trp Arg Arg Pro Arg Thr Glu Thr Gln Val1 5 104410PRTHuman papillomavirus 44Trp Lys Pro Thr Arg Arg Glu Thr Glu Val1 5 104510PRTHuman papillomavirus 45Arg Arg Thr Leu Arg Arg Glu Thr Gln Val1 5 104610PRTHuman papillomavirus 46Arg Arg Leu Thr Arg Arg Glu Thr Gln Val1 5 104710PRTHuman papillomavirus 47Arg Leu Arg Arg Arg Arg Glu Thr Gln Val1 5 104810PRTHuman papillomavirus 48Arg Leu Gln Arg Arg Asn Glu Thr Gln Val1 5 104910PRTHuman papillomavirus 49Arg Leu Gln Arg Arg Arg Val Thr Gln Val1 5 105010PRTHuman papillomavirus 50Thr Ser Arg Glu Pro Arg Glu Ser Thr Val1 5 105110PRTHuman papillomavirus 51Gln Arg Gln Ala Arg Ser Glu Thr Leu Val1 5 105210PRTHuman papillomavirus 52Arg Leu Gln Arg Arg Arg Gln Thr Gln Val1 5 105310PRTHuman papillomavirus 53Arg Leu Gln Arg Arg Arg Glu Thr Ala Leu1 5 105410PRTHuman papillomavirus 54Thr Ser Arg Gln Ala Thr Glu Ser Thr Val1 5 105510PRTHuman papillomavirus 55Arg Arg Arg Thr Arg Gln Glu Thr Gln Val1 5 105610PRTHuman papillomavirus 56Arg Arg Arg Glu Ala Thr Glu Thr Gln Val1 5 105725PRTHuman papillomavirus 57Phe Asp Asp Pro Lys Gln Arg Pro Tyr Lys Leu Pro Asp Leu Cys Thr1 5 10 15Glu Leu Asn Thr Ser Leu Gln Asp Val 20 255823PRTHuman papillomavirus 58Leu Leu Ile Arg Cys Leu Arg Cys Gln Lys Pro Leu Asn Pro Ala Glu1 5 10 15Lys Arg Arg His Leu Lys Asp 205924PRTHuman papillomavirus 59Arg His Leu Lys Asp Lys Arg Arg Phe His Ser Ile Ala Gly Gln Tyr1 5 10 15Arg Gly Gln Cys Asn Thr Cys Cys 206012PRTHuman papillomavirus 60Arg Pro Tyr Lys Leu Pro Asp Leu Cys Thr Glu Leu1 5 106112PRTHuman papillomavirus 61Leu Leu Ile Arg Cys Leu Arg Cys Gln Lys Pro Leu1 5 106212PRTHuman papillomavirus 62Arg His Leu Lys Asp Lys Arg Arg Phe His Ser Ile1 5 106310PRTHuman papillomavirus 63Arg Pro Arg Arg Gln Thr Glu Thr Gln Val1 5 106410PRTHuman papillomavirus 64Arg His Thr Thr Ala Thr Glu Ser Ala Val1 5 106510PRTHuman papillomavirus 65Thr Ser Arg Gln Ala Thr Glu Ser Thr Val1 5 106610PRTHuman papillomavirus 66Arg Cys Trp Arg Pro Ser Ala Thr Val Val1 5 106710PRTHuman papillomavirus 67Pro Pro Arg Gln Arg Ser Glu Thr Gln Val1 5 106872PRTHuman papillomavirus 68Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 706976PRTHuman papillomavirus 69Phe Ile His Thr Lys Leu Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr1 5 10 15Val Val Gly Gly Asp Glu Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu 20 25 30Val Leu Asp Gly Pro Ala Ala Leu Asp Gly Lys Met Glu Thr Gly Asp 35 40 45Val Ile Val Ser Val Asn Asp Thr Cys Val Leu Gly His Thr His Ala 50 55 60Gln Val Val Lys Ile Phe Gln Ser Ile Pro Ile Gly65 70 757085PRTHuman papillomavirus 70Phe Ile His Thr Lys Leu Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr1 5 10 15Val Val Gly Gly Asp Glu Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu 20 25 30Val Leu Asp Gly Pro Ala Ala Leu Asp Gly Lys Met Glu Thr Gly Asp 35 40 45Val Ile Val Ser Val Asn Asp Thr Cys Val Leu Gly His Thr His Ala 50 55 60Gln Val Val Lys Ile Phe Gln Ser Ile Pro Ile Gly Ala Ser Val Asp65 70 75 80Leu Glu Leu Cys Arg 857178PRTHuman papillomavirus 71Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu Pro1 5 10 15Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala Ala 20 25 30Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn Asp 35 40 45Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe Gln 50 55 60Ser Ile Pro Ile Gly Ala Ser Val Asp Leu Glu Leu Cys Arg65 70 757288PRTHuman papillomavirus 72Phe Ile His Thr Lys Leu Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr1 5 10 15Val Val Gly Gly Asp Glu Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu 20 25 30Val Leu Asp Gly Pro Ala Ala Leu Asp Gly Lys Met Glu Thr Gly Asp 35 40 45Val Ile Val Ser Val Asn Asp Thr Cys Val Leu Gly His Thr His Ala 50 55 60Gln Val Val Lys Ile Phe Gln Ser Ile Pro Ile Gly Ala Ser Val Asp65 70 75 80Leu Glu Leu Cys Arg Gly Tyr Pro 857388PRTHuman papillomavirus 73Lys Gly Lys Phe Ile His Thr Lys Leu Arg Lys Ser Ser Arg Gly Phe1 5 10 15Gly Phe Thr Val Val Gly Gly Asp Glu Pro Asp Glu Phe Leu Gln Ile 20 25 30Lys Ser Leu Val Leu Asp Gly Pro Ala Ala Leu Asp Gly Lys Met Glu 35 40 45Thr Gly Asp Val Ile Val Ser Val Asn Asp Thr Cys Val Leu Gly His 50 55 60Thr His Ala Gln Val Val Lys Ile Phe Gln Ser Ile Pro Ile Gly Ala65 70 75 80Ser Val Asp Leu Glu Leu Cys Arg 857481PRTHuman papillomavirus 74Lys Gly Lys Phe Ile His Thr Lys Leu Arg Lys Ser Ser Arg Gly Phe1 5 10 15Gly Phe Thr Val Val Gly Gly Asp Glu Pro Asp Glu Phe Leu Gln Ile 20 25 30Lys Ser Leu Val Leu Asp Gly Pro Ala Ala Leu Asp Gly Lys Met Glu 35 40 45Thr Gly Asp Val Ile Val Ser Val Asn Asp Thr Cys Val Leu Gly His 50 55 60Thr His Ala Gln Val Val Lys Ile Phe Gln Ser Ile Pro Ile Gly Ala65 70 75 80Ser7594PRTHuman papillomavirus 75Glu Leu Lys Gly Lys Phe Ile His Thr Lys Leu Arg Lys Ser Ser Arg1 5 10 15Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu Pro Asp Glu Phe Leu 20 25 30Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala Ala Leu Asp Gly Lys 35 40 45Met Glu Thr Gly Asp Val Ile Val Ser Val Asn Asp Thr Cys Val Leu 50 55 60Gly His Thr His Ala Gln Val Val Lys Ile Phe Gln Ser Ile Pro Ile65 70 75 80Gly Ala Ser Val Asp Leu Glu Leu Cys Arg Gly Tyr Pro Leu 85 907699PRTHuman papillomavirus 76Ser Glu Leu Lys Gly Lys Phe Ile His Thr Lys Leu Arg Lys Ser Ser1 5 10 15Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu Pro Asp Glu Phe 20 25 30Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala Ala Leu Asp Gly 35 40 45Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn Asp Thr Cys Val 50 55 60Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe Gln Ser Ile Pro65 70 75 80Ile Gly Ala Ser Val Asp Leu Glu Leu Cys Arg Gly Tyr Pro Leu Pro 85 90 95Phe Asp Pro7772PRTHuman papillomavirus 77Arg Lys Ser Ala Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 707872PRTHuman papillomavirus 78Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Glu Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 707972PRTHuman papillomavirus 79Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Leu Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 708072PRTHuman papillomavirus 80Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala

20 25 30Ser Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 708172PRTHuman papillomavirus 81Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Arg Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 708272PRTHuman papillomavirus 82Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ala Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 708372PRTHuman papillomavirus 83Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Glu Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 708472PRTHuman papillomavirus 84Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Leu Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 708572PRTHuman papillomavirus 85Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ser Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 708672PRTHuman papillomavirus 86Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Leu Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 708772PRTHuman papillomavirus 87Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ser Ser65 708872PRTHuman papillomavirus 88Arg Lys Ser Thr Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 708972PRTHuman papillomavirus 89Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Gly Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 709072PRTHuman papillomavirus 90Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Ala Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 709172PRTHuman papillomavirus 91Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Ala Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 709272PRTHuman papillomavirus 92Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Ala Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 709372PRTHuman papillomavirus 93Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Ala Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 709472PRTHuman papillomavirus 94Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Ala Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 709572PRTHuman papillomavirus 95Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Ala Ile Gly Ala Ser65 709672PRTHuman papillomavirus 96Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ala65 709772PRTHuman papillomavirus 97Arg Lys Ser Ser Ser Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 709872PRTHuman papillomavirus 98Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Leu Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 709972PRTHuman papillomavirus 99Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Thr Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 7010072PRTHuman papillomavirus 100Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Gly Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 7010172PRTHuman papillomavirus 101Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Ser Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 7010272PRTHuman papillomavirus 102Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Lys 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 7010372PRTHuman papillomavirus 103Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Phe His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 7010472PRTHuman papillomavirus 104Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Asn Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Gly Ala Ser65 7010572PRTHuman papillomavirus 105Arg Lys Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu1 5 10 15Pro Asp Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala 20 25 30Ala Leu Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn 35 40 45Asp Thr Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe 50 55 60Gln Ser Ile Pro Ile Ser Ala Ser65 7010693PRTHuman papillomavirus 106Leu Arg Lys Glu Pro Glu Ile Ile Thr Val Thr Leu Lys Lys Gln Asn1 5 10 15Gly Met Gly Leu Ser Ile Val Ala Ala Lys Gly Ala Gly Gln Asp Lys 20 25 30Leu Gly Ile Tyr Val Lys Ser Val Val Lys Gly Gly Ala Ala Asp Val 35 40 45Asp Gly Arg Leu Ala Ala Gly Asp Gln Leu Leu Ser Val Asp Gly Arg 50 55 60Ser Leu Val Gly Leu Ser Gln Glu Arg Ala Ala Glu Leu Met Thr Arg65 70 75 80Thr Ser Ser Val Val Thr Leu Glu Val Ala Lys Gln Gly 85 90107105PRTHuman papillomavirus 107Leu Ile Arg Pro Ser Val Ile Ser Ile Ile Gly Leu Tyr Lys Glu Lys1 5 10 15Gly Lys Gly Leu Gly Phe Ser Ile Ala Gly Gly Arg Asp Cys Ile Arg 20 25 30Gly Gln Met Gly Ile Phe Val Lys Thr Ile Phe Pro Asn Gly Ser Ala 35 40 45Ala Glu Asp Gly Arg Leu Lys Glu Gly Asp Glu Ile Leu Asp Val Asn 50 55 60Gly Ile Pro Ile Lys Gly Leu Thr Phe Gln Glu Ala Ile His Thr Phe65 70 75 80Lys Gln Ile Arg Ser Gly Leu Phe Val Leu Thr Val Arg Thr Lys Leu 85 90 95Val Ser Pro Ser Leu Thr Asn Ser Ser 100 105108105PRTHuman papillomavirus 108Gln Ser Glu Asn Glu Glu Asp Val Cys Phe Ile Val Leu Asn Arg Lys1 5 10 15Glu Gly Ser Gly Leu Gly Phe Ser Val Ala Gly Gly Thr Asp Val Glu 20 25 30Pro Lys Ser Ile Thr Val His Arg Val Phe Ser Gln Gly Ala Ala Ser 35 40 45Gln Glu Gly Thr Met Asn Arg Gly Asp Phe Leu Leu Ser Val Asn Gly 50 55 60Ala Ser Leu Ala Gly Leu Ala His Gly Asn Val Leu Lys Val Leu His65 70 75 80Gln Ala Gln Leu His Lys Asp Ala Leu Val Val Ile Lys Lys Gly Met 85 90 95Asp Gln Pro Arg Pro Ser Asn Ser Ser 100 105109132PRTHuman papillomavirus 109Gly Ile Ser Ser Leu Gly Arg Lys Thr Pro Gly Pro Lys Asp Arg Ile1 5 10 15Val Met Glu Val Thr Leu Asn Lys Glu Pro Arg Val Gly Leu Gly Ile 20 25 30Gly Ala Cys Cys Leu Ala Leu Glu Asn Ser Pro Pro Gly Ile Tyr Ile 35 40 45His Ser Leu Ala Pro Gly Ser Val Ala Lys Met Glu Ser Asn Leu Ser 50 55 60Arg Gly Asp Gln Ile Leu Glu Val Asn Ser Val Asn Val Arg His Ala65 70 75 80Ala Leu Ser Lys Val His Ala Ile Leu Ser Lys Cys Pro Pro Gly Pro 85 90 95Val Arg Leu Val Ile Gly Arg His Pro Asn Pro Lys Val Ser Glu Gln 100 105 110Glu Met Asp Glu Val Ile Ala Arg Ser Thr Tyr Gln Glu Ser Lys Glu 115 120 125Ala Asn Ser Ser 130110101PRTHuman papillomavirus 110Leu Gly Arg Ser Val Ala Val His Asp Ala Leu Cys Val Glu Val Leu1 5 10 15Lys Thr Ser Ala Gly Leu Gly Leu Ser Leu Asp Gly Gly Lys Ser Ser 20 25 30Val Thr Gly Asp Gly Pro Leu Val Ile Lys Arg Val Tyr Lys Gly Gly 35 40 45Ala Ala Glu Gln Ala Gly Ile Ile Glu Ala Gly Asp Glu Ile Leu Ala 50 55 60Ile Asn Gly Lys Pro Leu Val Gly Leu Met His Phe Asp Ala Trp Asn65 70 75 80Ile Met Lys Ser Val Pro Glu Gly Pro Val Gln Leu Leu Ile Arg Lys 85 90 95His Arg Asn Ser Ser 10011198PRTHuman papillomavirus 111Arg Glu Glu Gly Gly Met Pro Gln Thr Val Ile Leu Pro Gly Pro Ala1 5 10 15Pro Trp Gly Phe Arg Leu Ser Gly Gly Ile

Asp Phe Asn Gln Pro Leu 20 25 30Val Ile Thr Arg Ile Thr Pro Gly Ser Lys Ala Ala Ala Ala Asn Leu 35 40 45Cys Pro Gly Asp Val Ile Leu Ala Ile Asp Gly Phe Gly Thr Glu Ser 50 55 60Met Thr His Ala Asp Ala Gln Asp Arg Ile Lys Ala Ala Ala His Gln65 70 75 80Leu Cys Leu Lys Ile Asp Arg Gly Glu Thr His Leu Trp Ser Pro Asn 85 90 95Ser Ser11285PRTHuman papillomavirus 112Ile Leu Val Glu Val Gln Leu Ser Gly Gly Ala Pro Trp Gly Phe Thr1 5 10 15Leu Lys Gly Gly Arg Glu His Gly Glu Pro Leu Val Ile Thr Lys Ile 20 25 30Glu Glu Gly Ser Lys Ala Ala Ala Val Asp Lys Leu Leu Ala Gly Asp 35 40 45Glu Ile Val Gly Ile Asn Asp Ile Gly Leu Ser Gly Phe Arg Gln Glu 50 55 60Ala Ile Cys Leu Val Lys Gly Ser His Lys Thr Leu Lys Leu Val Val65 70 75 80Lys Arg Asn Ser Ser 85113106PRTHuman papillomavirus 113Ser Val Gly His Val Arg Gly Pro Gly Pro Ser Val Gln His Thr Thr1 5 10 15Leu Asn Gly Asp Ser Leu Thr Ser Gln Leu Thr Leu Leu Gly Gly Asn 20 25 30Ala Arg Gly Ser Phe Val His Ser Val Lys Pro Gly Ser Leu Ala Glu 35 40 45Lys Ala Gly Leu Arg Glu Gly His Gln Leu Leu Leu Leu Glu Gly Cys 50 55 60Ile Arg Gly Glu Arg Gln Ser Val Pro Leu Asp Thr Cys Thr Lys Glu65 70 75 80Glu Ala His Trp Thr Ile Gln Arg Cys Ser Gly Pro Val Thr Leu His 85 90 95Tyr Lys Val Asn His Glu Gly Tyr Arg Lys 100 105114105PRTHuman papillomavirus 114Arg Arg Pro Ala Arg Arg Ile Leu Ser Gln Val Thr Met Leu Ala Phe1 5 10 15Gln Gly Asp Ala Leu Leu Glu Gln Ile Ser Val Ile Gly Gly Asn Leu 20 25 30Thr Gly Ile Phe Ile His Arg Val Thr Pro Gly Ser Ala Ala Asp Gln 35 40 45Met Ala Leu Arg Pro Gly Thr Gln Ile Val Met Val Asp Tyr Glu Ala 50 55 60Ser Glu Pro Leu Phe Lys Ala Val Leu Glu Asp Thr Thr Leu Glu Glu65 70 75 80Ala Val Gly Leu Leu Arg Arg Val Asp Gly Phe Cys Cys Leu Ser Val 85 90 95Lys Val Asn Thr Asp Gly Tyr Lys Arg 100 105115100PRTHuman papillomavirus 115Ile Leu Ser Gln Val Thr Met Leu Ala Phe Gln Gly Asp Ala Leu Leu1 5 10 15Glu Gln Ile Ser Val Ile Gly Gly Asn Leu Thr Gly Ile Phe Ile His 20 25 30Arg Val Thr Pro Gly Ser Ala Ala Asp Gln Met Ala Leu Arg Pro Gly 35 40 45Thr Gln Ile Val Met Val Asp Tyr Glu Ala Ser Glu Pro Leu Phe Lys 50 55 60Ala Val Leu Glu Asp Thr Thr Leu Glu Glu Ala Val Gly Leu Leu Arg65 70 75 80Arg Val Asp Gly Phe Cys Cys Leu Ser Val Lys Val Asn Thr Asp Gly 85 90 95Tyr Lys Arg Leu 10011690PRTHuman papillomavirus 116Thr Arg Val Arg Leu Val Gln Phe Gln Lys Asn Thr Asp Glu Pro Met1 5 10 15Gly Ile Thr Leu Lys Met Asn Glu Leu Asn His Cys Ile Val Ala Arg 20 25 30Ile Met His Gly Gly Met Ile His Arg Gln Gly Thr Leu His Val Gly 35 40 45Asp Glu Ile Arg Glu Ile Asn Gly Ile Ser Val Ala Asn Gln Thr Val 50 55 60Glu Gln Leu Gln Lys Met Leu Arg Glu Met Arg Gly Ser Ile Thr Phe65 70 75 80Lys Ile Val Pro Ser Tyr Arg Thr Gln Ser 85 9011788PRTHuman papillomavirus 117Leu Glu Gln Lys Ala Val Leu Glu Gln Val Gln Leu Asp Ser Pro Leu1 5 10 15Gly Leu Glu Ile His Thr Thr Ser Asn Cys Gln His Phe Val Ser Gln 20 25 30Val Asp Thr Gln Val Pro Thr Asp Ser Arg Leu Gln Ile Gln Pro Gly 35 40 45Asp Glu Val Val Gln Ile Asn Glu Gln Val Val Val Gly Trp Pro Arg 50 55 60Lys Asn Met Val Arg Glu Leu Leu Arg Glu Pro Ala Gly Leu Ser Leu65 70 75 80Val Leu Lys Lys Ile Pro Ile Pro 8511892PRTHuman papillomavirus 118Gln Arg Lys Leu Val Thr Val Glu Lys Gln Asp Asn Glu Thr Phe Gly1 5 10 15Phe Glu Ile Gln Ser Tyr Arg Pro Gln Asn Gln Asn Ala Cys Ser Ser 20 25 30Glu Met Phe Thr Leu Ile Cys Lys Ile Gln Glu Asp Ser Pro Ala His 35 40 45Cys Ala Gly Leu Gln Ala Gly Asp Val Leu Ala Asn Ile Asn Gly Val 50 55 60Ser Thr Glu Gly Phe Thr Tyr Lys Gln Val Val Asp Leu Ile Arg Ser65 70 75 80Ser Gly Asn Leu Leu Thr Ile Glu Thr Leu Asn Gly 85 90119109PRTHuman papillomavirus 119Arg Cys Leu Ile Gln Thr Lys Gly Gln Arg Ser Met Asp Gly Tyr Pro1 5 10 15Glu Gln Phe Cys Val Arg Ile Glu Lys Asn Pro Gly Leu Gly Phe Ser 20 25 30Ile Ser Gly Gly Ile Ser Gly Gln Gly Asn Pro Phe Lys Pro Ser Asp 35 40 45Lys Gly Ile Phe Val Thr Arg Val Gln Pro Asp Gly Pro Ala Ser Asn 50 55 60Leu Leu Gln Pro Gly Asp Lys Ile Leu Gln Ala Asn Gly His Ser Phe65 70 75 80Val His Met Glu His Glu Lys Ala Val Leu Leu Leu Lys Ser Phe Gln 85 90 95Asn Thr Val Asp Leu Val Ile Gln Arg Glu Leu Thr Val 100 10512097PRTHuman papillomavirus 120Pro Thr Ser Pro Glu Ile Gln Glu Leu Arg Gln Met Leu Gln Ala Pro1 5 10 15His Phe Lys Gly Ala Thr Ile Lys Arg His Glu Met Thr Gly Asp Ile 20 25 30Leu Val Ala Arg Ile Ile His Gly Gly Leu Ala Glu Arg Ser Gly Leu 35 40 45Leu Tyr Ala Gly Asp Lys Leu Val Glu Val Asn Gly Val Ser Val Glu 50 55 60Gly Leu Asp Pro Glu Gln Val Ile His Ile Leu Ala Met Ser Arg Gly65 70 75 80Thr Ile Met Phe Lys Val Val Pro Val Ser Asp Pro Pro Val Asn Ser 85 90 95Ser121141PRTHuman papillomavirus 121Pro Thr Ser Pro Glu Ile Gln Glu Leu Arg Gln Met Leu Gln Ala Pro1 5 10 15His Phe Lys Ala Leu Leu Ser Ala His Asp Thr Ile Ala Gln Lys Asp 20 25 30Phe Glu Pro Leu Leu Pro Pro Leu Pro Asp Asn Ile Pro Glu Ser Glu 35 40 45Glu Ala Met Arg Ile Val Cys Leu Val Lys Asn Gln Gln Pro Leu Gly 50 55 60Ala Thr Ile Lys Arg His Glu Met Thr Gly Asp Ile Leu Val Ala Arg65 70 75 80Ile Ile His Gly Gly Leu Ala Glu Arg Ser Gly Leu Leu Tyr Ala Gly 85 90 95Asp Lys Leu Val Glu Val Asn Gly Val Ser Val Glu Gly Leu Asp Pro 100 105 110Glu Gln Val Ile His Ile Leu Ala Met Ser Arg Gly Thr Ile Met Phe 115 120 125Lys Val Val Pro Val Ser Asp Pro Pro Val Asn Ser Ser 130 135 140122101PRTHuman papillomavirus 122Ile Gln Val Asn Gly Thr Asp Ala Asp Tyr Glu Tyr Glu Glu Ile Thr1 5 10 15Leu Glu Arg Gly Asn Ser Gly Leu Gly Phe Ser Ile Ala Gly Gly Thr 20 25 30Asp Asn Pro His Ile Gly Asp Asp Ser Ser Ile Phe Ile Thr Lys Ile 35 40 45Ile Thr Gly Gly Ala Ala Ala Gln Asp Gly Arg Leu Arg Val Asn Asp 50 55 60Cys Ile Leu Gln Val Asn Glu Val Asp Val Arg Asp Val Thr His Ser65 70 75 80Lys Ala Val Glu Ala Leu Lys Glu Ala Gly Ser Ile Val Arg Leu Tyr 85 90 95Val Lys Arg Arg Asn 10012395PRTHuman papillomavirus 123Ile Gln Leu Ile Lys Gly Pro Lys Gly Leu Gly Phe Ser Ile Ala Gly1 5 10 15Gly Val Gly Asn Gln His Ile Pro Gly Asp Asn Ser Ile Tyr Val Thr 20 25 30Lys Ile Ile Glu Gly Gly Ala Ala His Lys Asp Gly Lys Leu Gln Ile 35 40 45Gly Asp Lys Leu Leu Ala Val Asn Asn Val Cys Leu Glu Glu Val Thr 50 55 60His Glu Glu Ala Val Thr Ala Leu Lys Asn Thr Ser Asp Phe Val Tyr65 70 75 80Leu Lys Val Ala Lys Pro Thr Ser Met Tyr Met Asn Asp Gly Asn 85 90 95124203PRTHuman papillomavirus 124Val Asn Gly Thr Asp Ala Asp Tyr Glu Tyr Glu Glu Ile Thr Leu Glu1 5 10 15Arg Gly Asn Ser Gly Leu Gly Phe Ser Ile Ala Gly Gly Thr Asp Asn 20 25 30Pro His Ile Gly Asp Asp Ser Ser Ile Phe Ile Thr Lys Ile Ile Thr 35 40 45Gly Gly Ala Ala Ala Gln Asp Gly Arg Leu Arg Val Asn Asp Cys Ile 50 55 60Leu Gln Val Asn Glu Val Asp Val Arg Asp Val Thr His Ser Lys Ala65 70 75 80Val Glu Ala Leu Lys Glu Ala Gly Ser Ile Val Arg Leu Tyr Val Lys 85 90 95Arg Arg Lys Pro Val Ser Glu Lys Ile Met Glu Ile Lys Leu Ile Lys 100 105 110Gly Pro Lys Gly Leu Gly Phe Ser Ile Ala Gly Gly Val Gly Asn Gln 115 120 125His Ile Pro Gly Asp Asn Ser Ile Tyr Val Thr Lys Ile Ile Glu Gly 130 135 140Gly Ala Ala His Lys Asp Gly Lys Leu Gln Ile Gly Asp Lys Leu Leu145 150 155 160Ala Val Asn Asn Val Cys Leu Glu Glu Val Thr His Glu Glu Ala Val 165 170 175Thr Ala Leu Lys Asn Thr Ser Asp Phe Val Tyr Leu Lys Val Ala Lys 180 185 190Pro Thr Ser Met Tyr Met Asn Asp Gly Tyr Ala 195 20012585PRTHuman papillomavirus 125Ile Leu His Arg Gly Ser Thr Gly Leu Gly Phe Asn Ile Val Gly Gly1 5 10 15Glu Asp Gly Glu Gly Ile Phe Ile Ser Phe Ile Leu Ala Gly Gly Pro 20 25 30Ala Asp Leu Ser Gly Glu Leu Arg Lys Gly Asp Arg Ile Ile Ser Val 35 40 45Asn Ser Val Asp Leu Arg Ala Ala Ser His Glu Gln Ala Ala Ala Ala 50 55 60Leu Lys Asn Ala Gly Gln Ala Val Thr Ile Val Ala Gln Tyr Arg Pro65 70 75 80Glu Glu Tyr Ser Arg 85126110PRTHuman papillomavirus 126Ile Glu Gly Arg Gly Ile Leu Glu Gly Glu Pro Arg Lys Val Val Leu1 5 10 15His Lys Gly Ser Thr Gly Leu Gly Phe Asn Ile Val Gly Gly Glu Asp 20 25 30Gly Glu Gly Ile Phe Val Ser Phe Ile Leu Ala Gly Gly Pro Ala Asp 35 40 45Leu Ser Gly Glu Leu Gln Arg Gly Asp Gln Ile Leu Ser Val Asn Gly 50 55 60Ile Asp Leu Arg Gly Ala Ser His Glu Gln Ala Ala Ala Ala Leu Lys65 70 75 80Gly Ala Gly Gln Thr Val Thr Ile Ile Ala Gln His Gln Pro Glu Asp 85 90 95Tyr Ala Arg Phe Glu Ala Lys Ile His Asp Leu Asn Ser Ser 100 105 110127101PRTHuman papillomavirus 127Ile Ser Tyr Val Asn Gly Thr Glu Ile Glu Tyr Glu Phe Glu Glu Ile1 5 10 15Thr Leu Glu Arg Gly Asn Ser Gly Leu Gly Phe Ser Ile Ala Gly Gly 20 25 30Thr Asp Asn Pro His Ile Gly Asp Asp Pro Gly Ile Phe Ile Thr Lys 35 40 45Ile Ile Pro Gly Gly Ala Ala Ala Glu Asp Gly Arg Leu Arg Val Asn 50 55 60Asp Cys Ile Leu Arg Val Asn Glu Val Asp Val Ser Glu Val Ser His65 70 75 80Ser Lys Ala Val Glu Ala Leu Lys Glu Ala Gly Ser Ile Val Arg Leu 85 90 95Tyr Val Arg Arg Arg 100128113PRTHuman papillomavirus 128Ile Pro Ile Leu Glu Thr Val Val Glu Ile Lys Leu Phe Lys Gly Pro1 5 10 15Lys Gly Leu Gly Phe Ser Ile Ala Gly Gly Val Gly Asn Gln His Ile 20 25 30Pro Gly Asp Asn Ser Ile Tyr Val Thr Lys Ile Ile Asp Gly Gly Ala 35 40 45Ala Gln Lys Asp Gly Arg Leu Gln Val Gly Asp Arg Leu Leu Met Val 50 55 60Asn Asn Tyr Ser Leu Glu Glu Val Thr His Glu Glu Ala Val Ala Ile65 70 75 80Leu Lys Asn Thr Ser Glu Val Val Tyr Leu Lys Val Gly Lys Pro Thr 85 90 95Thr Ile Tyr Met Thr Asp Pro Tyr Gly Pro Pro Asn Ser Ser Leu Thr 100 105 110Asp129101PRTHuman papillomavirus 129Gly Ile Pro Tyr Val Glu Glu Pro Arg His Val Lys Val Gln Lys Gly1 5 10 15Ser Glu Pro Leu Gly Ile Ser Ile Val Ser Gly Glu Lys Gly Gly Ile 20 25 30Tyr Val Ser Lys Val Thr Val Gly Ser Ile Ala His Gln Ala Gly Leu 35 40 45Glu Tyr Gly Asp Gln Leu Leu Glu Phe Asn Gly Ile Asn Leu Arg Ser 50 55 60Ala Thr Glu Gln Gln Ala Arg Leu Ile Ile Gly Gln Gln Cys Asp Thr65 70 75 80Ile Thr Ile Leu Ala Gln Tyr Asn Pro His Val His Gln Leu Arg Asn 85 90 95Ser Ser Leu Thr Asp 100130103PRTHuman papillomavirus 130Gly Ile Leu Ala Gly Asp Ala Asn Lys Lys Thr Leu Glu Pro Arg Val1 5 10 15Val Phe Ile Lys Lys Ser Gln Leu Glu Leu Gly Val His Leu Cys Gly 20 25 30Gly Asn Leu His Gly Val Phe Val Ala Glu Val Glu Asp Asp Ser Pro 35 40 45Ala Lys Gly Pro Asp Gly Leu Val Pro Gly Asp Leu Ile Leu Glu Tyr 50 55 60Gly Ser Leu Asp Val Arg Asn Lys Thr Val Glu Glu Val Tyr Val Glu65 70 75 80Met Leu Lys Pro Arg Asp Gly Val Arg Leu Lys Val Gln Tyr Arg Pro 85 90 95Glu Glu Phe Ile Val Thr Asp 10013193PRTHuman papillomavirus 131Leu Asn Ile Val Thr Val Thr Leu Asn Met Glu Arg His His Phe Leu1 5 10 15Gly Ile Ser Ile Val Gly Gln Ser Asn Asp Arg Gly Asp Gly Gly Ile 20 25 30Tyr Ile Gly Ser Ile Met Lys Gly Gly Ala Val Ala Ala Asp Gly Arg 35 40 45Ile Glu Pro Gly Asp Met Leu Leu Gln Val Asn Asp Val Asn Phe Glu 50 55 60Asn Met Ser Asn Asp Asp Ala Val Arg Val Leu Arg Glu Ile Val Ser65 70 75 80Gln Thr Gly Pro Ile Ser Leu Thr Val Ala Lys Cys Trp 85 90132100PRTHuman papillomavirus 132Leu Asn Ile Ile Thr Val Thr Leu Asn Met Glu Lys Tyr Asn Phe Leu1 5 10 15Gly Ile Ser Ile Val Gly Gln Ser Asn Glu Arg Gly Asp Gly Gly Ile 20 25 30Tyr Ile Gly Ser Ile Met Lys Gly Gly Ala Val Ala Ala Asp Gly Arg 35 40 45Ile Glu Pro Gly Asp Met Leu Leu Gln Val Asn Asp Met Asn Phe Glu 50 55 60Asn Met Ser Asn Asp Asp Ala Val Arg Val Leu Arg Asp Ile Val His65 70 75 80Lys Pro Gly Pro Ile Val Leu Thr Val Ala Lys Cys Trp Asp Pro Ser 85 90 95Pro Gln Asn Ser 10013395PRTHuman papillomavirus 133Ile Ile Thr Val Thr Leu Asn Met Glu Lys Tyr Asn Phe Leu Gly Ile1 5 10 15Ser Ile Val Gly Gln Ser Asn Glu Arg Gly Asp Gly Gly Ile Tyr Ile 20 25 30Gly Ser Ile Met Lys Gly Gly Ala Val Ala Ala Asp Gly Arg Ile Glu 35 40 45Pro Gly Asp Met Leu Leu Gln Val Asn Glu Ile Asn Phe Glu Asn Met 50 55 60Ser Asn Asp Asp Ala Val Arg Val Leu Arg Glu Ile Val His Lys Pro65 70 75 80Gly Pro Ile Thr Leu Thr Val Ala Lys Cys Trp Asp Pro Ser Pro 85 90

9513498PRTHuman papillomavirus 134Gln Gln Arg Glu Leu Arg Pro Arg Leu Cys Thr Met Lys Lys Gly Pro1 5 10 15Ser Gly Tyr Gly Phe Asn Leu His Ser Asp Lys Ser Lys Pro Gly Gln 20 25 30Phe Ile Arg Ser Val Asp Pro Asp Ser Pro Ala Glu Ala Ser Gly Leu 35 40 45Arg Ala Gln Asp Arg Ile Val Glu Val Asn Gly Val Cys Met Glu Gly 50 55 60Lys Gln His Gly Asp Val Val Ser Ala Ile Arg Ala Gly Gly Asp Glu65 70 75 80Thr Lys Leu Leu Val Val Asp Arg Glu Thr Asp Glu Phe Phe Lys Asn 85 90 95Ser Ser135155PRTHuman papillomavirus 135Gly Ile Gln Met Ser Ala Asp Ala Ala Ala Gly Ala Pro Leu Pro Arg1 5 10 15Leu Cys Cys Leu Glu Lys Gly Pro Asn Gly Tyr Gly Phe His Leu His 20 25 30Gly Glu Lys Gly Lys Leu Gly Gln Tyr Ile Arg Leu Val Glu Pro Gly 35 40 45Ser Pro Ala Glu Lys Ala Gly Leu Leu Ala Gly Asp Arg Leu Val Glu 50 55 60Val Asn Gly Glu Asn Val Glu Lys Glu Thr His Gln Gln Val Val Ser65 70 75 80Arg Ile Arg Ala Ala Leu Asn Ala Val Arg Leu Leu Val Val Asp Pro 85 90 95Glu Thr Asp Glu Gln Leu Gln Lys Leu Gly Val Gln Val Arg Glu Glu 100 105 110Leu Leu Arg Ala Gln Glu Ala Pro Gly Gln Ala Glu Pro Pro Ala Ala 115 120 125Ala Glu Val Gln Gly Ala Gly Asn Glu Asn Glu Pro Arg Glu Ala Asp 130 135 140Lys Ser His Pro Glu Gln Arg Glu Leu Arg Asn145 150 155136243PRTHuman papillomavirus 136Gly Ile Gln Met Ser Ala Asp Ala Ala Ala Gly Ala Pro Leu Pro Arg1 5 10 15Leu Cys Cys Leu Glu Lys Gly Pro Asn Gly Tyr Gly Phe His Leu His 20 25 30Gly Glu Lys Gly Lys Leu Gly Gln Tyr Ile Arg Leu Val Glu Pro Gly 35 40 45Ser Pro Ala Glu Lys Ala Gly Leu Leu Ala Gly Asp Arg Leu Val Glu 50 55 60Val Asn Gly Glu Asn Val Glu Lys Glu Thr His Gln Gln Val Val Ser65 70 75 80Arg Ile Arg Ala Ala Leu Asn Ala Val Arg Leu Leu Val Val Asp Pro 85 90 95Glu Thr Asp Glu Gln Leu Gln Lys Leu Gly Val Gln Val Arg Glu Glu 100 105 110Leu Leu Arg Ala Gln Glu Ala Pro Gly Gln Ala Glu Pro Pro Ala Ala 115 120 125Ala Glu Val Gln Gly Ala Gly Asn Glu Asn Glu Pro Arg Glu Ala Asp 130 135 140Lys Ser His Pro Glu Gln Arg Glu Leu Arg Pro Arg Leu Cys Thr Met145 150 155 160Lys Lys Gly Pro Ser Gly Tyr Gly Phe Asn Leu His Ser Asp Lys Ser 165 170 175Lys Pro Gly Gln Phe Ile Arg Ser Val Asp Pro Asp Ser Pro Ala Glu 180 185 190Ala Ser Gly Leu Arg Ala Gln Asp Arg Ile Val Glu Val Asn Gly Val 195 200 205Cys Met Glu Gly Lys Gln His Gly Asp Val Val Ser Ala Ile Arg Ala 210 215 220Gly Gly Asp Glu Thr Lys Leu Leu Val Val Asp Arg Glu Thr Asp Glu225 230 235 240Phe Phe Lys137155PRTHuman papillomavirus 137Gln Met Ser Ala Asp Ala Ala Ala Gly Ala Pro Leu Pro Arg Leu Cys1 5 10 15Cys Leu Glu Lys Gly Pro Asn Gly Tyr Gly Phe His Leu His Gly Glu 20 25 30Lys Gly Lys Leu Gly Gln Tyr Ile Arg Leu Val Glu Pro Gly Ser Pro 35 40 45Ala Glu Lys Ala Gly Leu Leu Ala Gly Asp Arg Leu Val Glu Val Asn 50 55 60Gly Glu Asn Val Glu Lys Glu Thr His Gln Gln Val Val Ser Arg Ile65 70 75 80Arg Ala Ala Leu Asn Ala Val Arg Leu Leu Val Val Asp Pro Glu Thr 85 90 95Asp Glu Gln Leu Gln Lys Leu Gly Val Gln Val Arg Glu Glu Leu Leu 100 105 110Arg Ala Gln Glu Ala Pro Gly Gln Ala Glu Pro Pro Ala Ala Ala Glu 115 120 125Val Gln Gly Ala Gly Asn Glu Asn Glu Pro Arg Glu Ala Asp Lys Ser 130 135 140His Pro Glu Gln Arg Glu Leu Arg Asn Ser Ser145 150 15513898PRTHuman papillomavirus 138Leu Thr Thr Gln Gln Ile Asp Leu Gln Gly Pro Gly Pro Trp Gly Phe1 5 10 15Arg Leu Val Gly Gly Lys Asp Phe Glu Gln Pro Leu Ala Ile Ser Arg 20 25 30Val Thr Pro Gly Ser Lys Ala Ala Leu Ala Asn Leu Cys Ile Gly Asp 35 40 45Val Ile Thr Ala Ile Asp Gly Glu Asn Thr Ser Asn Met Thr His Leu 50 55 60Glu Ala Gln Asn Arg Ile Lys Gly Cys Thr Asp Asn Leu Thr Leu Thr65 70 75 80Val Ala Arg Ser Glu His Lys Val Trp Ser Pro Leu Val Thr Asn Ser 85 90 95Ser Trp13989PRTHuman papillomavirus 139Ile Phe Met Asp Ser Phe Lys Val Val Leu Glu Gly Pro Ala Pro Trp1 5 10 15Gly Phe Arg Leu Gln Gly Gly Lys Asp Phe Asn Val Pro Leu Ser Ile 20 25 30Ser Arg Leu Thr Pro Gly Gly Lys Ala Ala Gln Ala Gly Val Ala Val 35 40 45Gly Asp Trp Val Leu Ser Ile Asp Gly Glu Asn Ala Gly Ser Leu Thr 50 55 60His Ile Glu Ala Gln Asn Lys Ile Arg Ala Cys Gly Glu Arg Leu Ser65 70 75 80Leu Gly Leu Ser Arg Ala Gln Pro Val 85140100PRTHuman papillomavirus 140Gln Gly His Glu Leu Ala Lys Gln Glu Ile Arg Val Arg Val Glu Lys1 5 10 15Asp Pro Glu Leu Gly Phe Ser Ile Ser Gly Gly Val Gly Gly Arg Gly 20 25 30Asn Pro Phe Arg Pro Asp Asp Asp Gly Ile Phe Val Thr Arg Val Gln 35 40 45Pro Glu Gly Pro Ala Ser Lys Leu Leu Gln Pro Gly Asp Lys Ile Ile 50 55 60Gln Ala Asn Gly Tyr Ser Phe Ile Asn Ile Glu His Gly Gln Ala Val65 70 75 80Ser Leu Leu Lys Thr Phe Gln Asn Thr Val Glu Leu Ile Ile Val Arg 85 90 95Glu Val Ser Ser 100141107PRTHuman papillomavirus 141Lys Asn Pro Ser Gly Glu Leu Lys Thr Val Thr Leu Ser Lys Met Lys1 5 10 15Gln Ser Leu Gly Ile Ser Ile Ser Gly Gly Ile Glu Ser Lys Val Gln 20 25 30Pro Met Val Lys Ile Glu Lys Ile Phe Pro Gly Gly Ala Ala Phe Leu 35 40 45Ser Gly Ala Leu Gln Ala Gly Phe Glu Leu Val Ala Val Asp Gly Glu 50 55 60Asn Leu Glu Gln Val Thr His Gln Arg Ala Val Asp Thr Ile Arg Arg65 70 75 80Ala Tyr Arg Asn Lys Ala Arg Glu Pro Met Glu Leu Val Val Arg Val 85 90 95Pro Gly Pro Ser Pro Arg Pro Ser Pro Ser Asp 100 10514297PRTHuman papillomavirus 142Glu Gly His Ser His Pro Arg Val Val Glu Leu Pro Lys Thr Glu Glu1 5 10 15Gly Leu Gly Phe Asn Ile Met Gly Gly Lys Glu Gln Asn Ser Pro Ile 20 25 30Tyr Ile Ser Arg Ile Ile Pro Gly Gly Ile Ala Asp Arg His Gly Gly 35 40 45Leu Lys Arg Gly Asp Gln Leu Leu Ser Val Asn Gly Val Ser Val Glu 50 55 60Gly Glu His His Glu Lys Ala Val Glu Leu Leu Lys Ala Ala Gln Gly65 70 75 80Lys Val Lys Leu Val Val Arg Tyr Thr Pro Lys Val Leu Glu Glu Met 85 90 95Glu14388PRTHuman papillomavirus 143Pro Gly Ala Pro Tyr Ala Arg Lys Thr Phe Thr Ile Val Gly Asp Ala1 5 10 15Val Gly Trp Gly Phe Val Val Arg Gly Ser Lys Pro Cys His Ile Gln 20 25 30Ala Val Asp Pro Ser Gly Pro Ala Ala Ala Ala Gly Met Lys Val Cys 35 40 45Gln Phe Val Val Ser Val Asn Gly Leu Asn Val Leu His Val Asp Tyr 50 55 60Arg Thr Val Ser Asn Leu Ile Leu Thr Gly Pro Arg Thr Ile Val Met65 70 75 80Glu Val Met Glu Glu Leu Glu Cys 8514497PRTHuman papillomavirus 144Gly Gln Tyr Gly Gly Glu Thr Val Lys Ile Val Arg Ile Glu Lys Ala1 5 10 15Arg Asp Ile Pro Leu Gly Ala Thr Val Arg Asn Glu Met Asp Ser Val 20 25 30Ile Ile Ser Arg Ile Val Lys Gly Gly Ala Ala Glu Lys Ser Gly Leu 35 40 45Leu His Glu Gly Asp Glu Val Leu Glu Ile Asn Gly Ile Glu Ile Arg 50 55 60Gly Lys Asp Val Asn Glu Val Phe Asp Leu Leu Ser Asp Met His Gly65 70 75 80Thr Leu Thr Phe Val Leu Ile Pro Ser Gln Gln Ile Lys Pro Pro Pro 85 90 95Ala145104PRTHuman papillomavirus 145Lys Pro Ser Gln Ala Ser Gly His Phe Ser Val Glu Leu Val Arg Gly1 5 10 15Tyr Ala Gly Phe Gly Leu Thr Leu Gly Gly Gly Arg Asp Val Ala Gly 20 25 30Asp Thr Pro Leu Ala Val Arg Gly Leu Leu Lys Asp Gly Pro Ala Gln 35 40 45Arg Cys Gly Arg Leu Glu Val Gly Asp Leu Val Leu His Ile Asn Gly 50 55 60Glu Ser Thr Gln Gly Leu Thr His Ala Gln Ala Val Glu Arg Ile Arg65 70 75 80Ala Gly Gly Pro Gln Leu His Leu Val Ile Arg Arg Pro Leu Glu Thr 85 90 95His Pro Gly Lys Pro Arg Gly Val 100146101PRTHuman papillomavirus 146Pro Val Met Ser Gln Cys Ala Cys Leu Glu Glu Val His Leu Pro Asn1 5 10 15Ile Lys Pro Gly Glu Gly Leu Gly Met Tyr Ile Lys Ser Thr Tyr Asp 20 25 30Gly Leu His Val Ile Thr Gly Thr Thr Glu Asn Ser Pro Ala Asp Arg 35 40 45Ser Gln Lys Ile His Ala Gly Asp Glu Val Thr Gln Val Asn Gln Gln 50 55 60Thr Val Val Gly Trp Gln Leu Lys Asn Leu Val Lys Lys Leu Arg Glu65 70 75 80Asn Pro Thr Gly Val Val Leu Leu Leu Lys Lys Arg Pro Thr Gly Ser 85 90 95Phe Asn Phe Thr Pro 10014797PRTHuman papillomavirus 147Ile Asp Asp Glu Glu Asp Ser Val Lys Ile Ile Arg Leu Val Lys Asn1 5 10 15Arg Glu Pro Leu Gly Ala Thr Ile Lys Lys Asp Glu Gln Thr Gly Ala 20 25 30Ile Ile Val Ala Arg Ile Met Arg Gly Gly Ala Ala Asp Arg Ser Gly 35 40 45Leu Ile His Val Gly Asp Glu Leu Arg Glu Val Asn Gly Ile Pro Val 50 55 60Glu Asp Lys Arg Pro Glu Glu Ile Ile Gln Ile Leu Ala Gln Ser Gln65 70 75 80Gly Ala Ile Thr Phe Lys Ile Ile Pro Gly Ser Lys Glu Glu Thr Pro 85 90 95Ser148452PRTHuman papillomavirus 148Met Gly Ser Ser Gln Ser Val Glu Ile Pro Gly Gly Gly Thr Glu Gly1 5 10 15Tyr His Val Leu Arg Val Gln Glu Asn Ser Pro Gly His Arg Ala Gly 20 25 30Leu Glu Pro Phe Phe Asp Phe Ile Val Ser Ile Asn Gly Ser Arg Leu 35 40 45Asn Lys Asp Asn Asp Thr Leu Lys Asp Leu Leu Lys Ala Asn Val Glu 50 55 60Lys Pro Val Lys Met Leu Ile Tyr Ser Ser Lys Thr Leu Glu Leu Arg65 70 75 80Glu Thr Ser Val Thr Pro Ser Asn Leu Trp Gly Gly Gln Gly Leu Leu 85 90 95Gly Val Ser Ile Arg Phe Cys Ser Phe Asp Gly Ala Asn Glu Asn Val 100 105 110Trp His Val Leu Glu Val Glu Ser Asn Ser Pro Ala Ala Leu Ala Gly 115 120 125Leu Arg Pro His Ser Asp Tyr Ile Ile Gly Ala Asp Thr Val Met Asn 130 135 140Glu Ser Glu Asp Leu Phe Ser Leu Ile Glu Thr His Glu Ala Lys Pro145 150 155 160Leu Lys Leu Tyr Val Tyr Asn Thr Asp Thr Asp Asn Cys Arg Glu Val 165 170 175Ile Ile Thr Pro Asn Ser Ala Trp Gly Gly Glu Gly Ser Leu Gly Cys 180 185 190Gly Ile Gly Tyr Gly Tyr Leu His Arg Ile Pro Thr Arg Pro Phe Glu 195 200 205Glu Gly Lys Lys Ile Ser Leu Pro Gly Gln Met Ala Gly Thr Pro Ile 210 215 220Thr Pro Leu Lys Asp Gly Phe Thr Glu Val Gln Leu Ser Ser Val Asn225 230 235 240Pro Pro Ser Leu Ser Pro Pro Gly Thr Thr Gly Ile Glu Gln Ser Leu 245 250 255Thr Gly Leu Ser Ile Ser Ser Thr Pro Pro Ala Val Ser Ser Val Leu 260 265 270Ser Thr Gly Val Pro Thr Val Pro Leu Leu Pro Pro Gln Val Asn Gln 275 280 285Ser Leu Thr Ser Val Pro Pro Met Asn Pro Ala Thr Thr Leu Pro Gly 290 295 300Leu Met Pro Leu Pro Ala Gly Leu Pro Asn Leu Pro Asn Leu Asn Leu305 310 315 320Asn Leu Pro Ala Pro His Ile Met Pro Gly Val Gly Leu Pro Glu Leu 325 330 335Val Asn Pro Gly Leu Pro Pro Leu Pro Ser Met Pro Pro Arg Asn Leu 340 345 350Pro Gly Ile Ala Pro Leu Pro Leu Pro Ser Glu Phe Leu Pro Ser Phe 355 360 365Pro Leu Val Pro Glu Ser Ser Ser Ala Ala Ser Ser Gly Glu Leu Leu 370 375 380Ser Ser Leu Pro Pro Thr Ser Asn Ala Pro Ser Asp Pro Ala Thr Thr385 390 395 400Thr Ala Lys Ala Asp Ala Ala Ser Ser Leu Thr Val Asp Val Thr Pro 405 410 415Pro Thr Ala Lys Ala Pro Thr Thr Val Glu Asp Arg Val Gly Asp Ser 420 425 430Thr Pro Val Ser Glu Lys Pro Val Ser Ala Ala Val Asp Ala Asn Ala 435 440 445Ser Glu Ser Pro 45014997PRTHuman papillomavirus 149Asn Glu Asn Val Trp His Val Leu Glu Val Glu Ser Asn Ser Pro Ala1 5 10 15Ala Leu Ala Gly Leu Arg Pro His Ser Asp Tyr Ile Ile Gly Ala Asp 20 25 30Thr Val Met Asn Glu Ser Glu Asp Leu Phe Ser Leu Ile Glu Thr His 35 40 45Glu Ala Lys Pro Leu Lys Leu Tyr Val Tyr Asn Thr Asp Thr Asp Asn 50 55 60Cys Arg Glu Val Ile Ile Thr Pro Asn Ser Ala Trp Gly Gly Glu Gly65 70 75 80Ser Leu Gly Cys Gly Ile Gly Tyr Gly Tyr Leu His Arg Ile Pro Thr85 90 95Arg150110PRTHuman papillomavirus 150Met Gly Ser Ser Gln Ser Val Glu Ile Pro Gly Gly Gly Thr Glu Gly1 5 10 15Tyr His Val Leu Arg Val Gln Glu Asn Ser Pro Gly His Arg Ala Gly 20 25 30Leu Glu Pro Phe Phe Asp Phe Ile Val Ser Ile Asn Gly Ser Arg Leu 35 40 45Asn Lys Asp Asn Asp Thr Leu Lys Asp Leu Leu Lys Ala Asn Val Glu 50 55 60Lys Pro Val Lys Met Leu Ile Tyr Ser Ser Lys Thr Leu Glu Leu Arg65 70 75 80Glu Thr Ser Val Thr Pro Ser Asn Leu Trp Gly Gly Gln Gly Leu Leu 85 90 95Gly Val Ser Ile Arg Phe Cys Ser Phe Asp Gly Ala Asn Glu 100 105 11015199PRTHuman papillomavirus 151Arg Ala Ser Glu Gln Val Trp His Val Leu Asp Val Glu Pro Ser Ser1 5 10 15Pro Ala Ala Leu Ala Gly Leu Arg Pro Tyr Thr Asp Tyr Val Val Gly 20 25 30Ser Asp Gln Ile Leu Gln Glu Ser Glu Asp Phe Phe Thr Leu Ile Glu 35 40 45Ser His Glu Gly Lys Pro Leu Lys Leu Met Val Tyr Asn Ser Lys Ser 50 55 60Asp Ser Cys Arg Glu Val Thr Val Thr Pro Asn Ala Ala Trp Gly Gly65 70 75 80Glu Gly Ser Leu Gly Cys Gly Ile Gly Tyr Gly Tyr Leu His Arg Ile 85 90 95Pro Thr Gln152110PRTHuman papillomavirus 152Met Gly Leu Gly Val Ser Ala Glu Gln Pro Ala Gly Gly Ala Glu Gly1 5 10 15Phe His Leu His Gly Val Gln Glu Asn

Ser Pro Ala Gln Gln Ala Gly 20 25 30Leu Glu Pro Tyr Phe Asp Phe Ile Ile Thr Ile Gly His Ser Arg Leu 35 40 45Asn Lys Glu Asn Asp Thr Leu Lys Ala Leu Leu Lys Ala Asn Val Glu 50 55 60Lys Pro Val Lys Leu Glu Val Phe Asn Met Lys Thr Met Arg Val Arg65 70 75 80Glu Val Glu Val Val Pro Ser Asn Met Trp Gly Gly Gln Gly Leu Leu 85 90 95Gly Ala Ser Val Arg Phe Cys Ser Phe Arg Arg Ala Ser Glu 100 105 110153440PRTHuman papillomavirus 153Met Gly Leu Gly Val Ser Ala Glu Gln Pro Ala Gly Gly Ala Glu Gly1 5 10 15Phe His Leu His Gly Val Gln Glu Asn Ser Pro Ala Gln Gln Ala Gly 20 25 30Leu Glu Pro Tyr Phe Asp Phe Ile Ile Thr Ile Gly His Ser Arg Leu 35 40 45Asn Lys Glu Asn Asp Thr Leu Lys Ala Leu Leu Lys Ala Asn Val Glu 50 55 60Lys Pro Val Lys Leu Glu Val Phe Asn Met Lys Thr Met Arg Val Arg65 70 75 80Glu Val Glu Val Val Pro Ser Asn Met Trp Gly Gly Gln Gly Leu Leu 85 90 95Gly Ala Ser Val Arg Phe Cys Ser Phe Arg Arg Ala Ser Glu Gln Val 100 105 110Trp His Val Leu Asp Val Glu Pro Ser Ser Pro Ala Ala Leu Ala Gly 115 120 125Leu Arg Pro Tyr Thr Asp Tyr Val Val Gly Ser Asp Gln Ile Leu Gln 130 135 140Glu Ser Glu Asp Phe Phe Thr Leu Ile Glu Ser His Glu Gly Lys Pro145 150 155 160Leu Lys Leu Met Val Tyr Asn Ser Lys Ser Asp Ser Cys Arg Glu Val 165 170 175Thr Val Thr Pro Asn Ala Ala Trp Gly Gly Glu Gly Ser Leu Gly Cys 180 185 190Gly Ile Gly Tyr Gly Tyr Leu His Arg Ile Pro Thr Gln Pro Pro Ser 195 200 205Tyr His Lys Lys Pro Pro Gly Thr Pro Pro Pro Ser Ala Leu Pro Leu 210 215 220Gly Ala Pro Pro Pro Asp Ala Leu Pro Pro Gly Pro Thr Pro Glu Asp225 230 235 240Ser Pro Ser Leu Glu Thr Gly Ser Arg Gln Ser Asp Tyr Met Glu Ala 245 250 255Leu Leu Gln Ala Pro Gly Ser Ser Met Glu Asp Pro Leu Pro Gly Pro 260 265 270Gly Ser Pro Ser His Ser Ala Pro Asp Pro Asp Gly Leu Pro His Phe 275 280 285Met Glu Thr Pro Leu Gln Pro Pro Pro Pro Val Gln Arg Val Met Asp 290 295 300Pro Gly Phe Leu Asp Val Ser Gly Ile Ser Leu Leu Asp Asn Ser Asn305 310 315 320Ala Ser Val Trp Pro Ser Leu Pro Ser Ser Thr Glu Leu Thr Thr Thr 325 330 335Ala Val Ser Thr Ser Gly Pro Glu Asp Ile Cys Ser Ser Ser Ser Ser 340 345 350His Glu Arg Gly Gly Glu Ala Thr Trp Ser Gly Ser Glu Phe Glu Val 355 360 365Ser Phe Leu Asp Ser Pro Gly Ala Gln Ala Gln Ala Asp His Leu Pro 370 375 380Gln Leu Thr Leu Pro Asp Ser Leu Thr Ser Ala Ala Ser Pro Glu Asp385 390 395 400Gly Leu Ser Ala Glu Leu Leu Glu Ala Gln Ala Glu Glu Glu Pro Ala 405 410 415Ser Thr Glu Gly Leu Asp Thr Gly Thr Glu Ala Glu Gly Leu Asp Ser 420 425 430Gln Ala Gln Ile Ser Thr Thr Glu 435 44015490PRTHuman papillomavirus 154Ile Tyr Thr Val Glu Leu Lys Arg Tyr Gly Gly Pro Leu Gly Ile Thr1 5 10 15Ile Ser Gly Thr Glu Glu Pro Phe Asp Pro Ile Ile Ile Ser Ser Leu 20 25 30Thr Lys Gly Gly Leu Ala Glu Arg Thr Gly Ala Ile His Ile Gly Asp 35 40 45Arg Ile Leu Ala Ile Asn Ser Ser Ser Leu Lys Gly Lys Pro Leu Ser 50 55 60Glu Ala Ile His Leu Leu Gln Met Ala Gly Glu Thr Val Thr Leu Lys65 70 75 80Ile Lys Lys Gln Thr Asp Ala Gln Ser Ala 85 9015583PRTHuman papillomavirus 155Val Val Glu Leu Met Lys Lys Glu Gly Thr Thr Leu Gly Leu Thr Val1 5 10 15Ser Gly Gly Ile Asp Lys Asp Gly Lys Pro Arg Val Ser Asn Leu Arg 20 25 30Gln Gly Gly Ile Ala Ala Arg Ser Asp Gln Leu Asp Val Gly Asp Tyr 35 40 45Ile Lys Ala Val Asn Gly Ile Asn Leu Ala Lys Phe Arg His Asp Glu 50 55 60Ile Ile Ser Leu Leu Lys Asn Val Gly Glu Arg Val Val Leu Glu Val65 70 75 80Glu Tyr Glu156106PRTHuman papillomavirus 156His Val Ala Thr Ala Ser Gly Pro Leu Leu Val Glu Val Ala Lys Thr1 5 10 15Pro Gly Ala Ser Leu Gly Val Ala Leu Thr Thr Ser Met Cys Cys Asn 20 25 30Lys Gln Val Ile Val Ile Asp Lys Ile Lys Ser Ala Ser Ile Ala Asp 35 40 45Arg Cys Gly Ala Leu His Val Gly Asp His Ile Leu Ser Ile Asp Gly 50 55 60Thr Ser Met Glu Tyr Cys Thr Leu Ala Glu Ala Thr Gln Phe Leu Ala65 70 75 80Asn Thr Thr Asp Gln Val Lys Leu Glu Ile Leu Pro His His Gln Thr 85 90 95Arg Leu Ala Leu Lys Gly Pro Asn Ser Ser 100 10515795PRTHuman papillomavirus 157Ile Met Ser Pro Thr Pro Val Glu Leu His Lys Val Thr Leu Tyr Lys1 5 10 15Asp Ser Asp Met Glu Asp Phe Gly Phe Ser Val Ala Asp Gly Leu Leu 20 25 30Glu Lys Gly Val Tyr Val Lys Asn Ile Arg Pro Ala Gly Pro Gly Asp 35 40 45Leu Gly Gly Leu Lys Pro Tyr Asp Arg Leu Leu Gln Val Asn His Val 50 55 60Arg Thr Arg Asp Phe Asp Cys Cys Leu Val Val Pro Leu Ile Ala Glu65 70 75 80Ser Gly Asn Lys Leu Asp Leu Val Ile Ser Arg Asn Pro Leu Ala 85 90 9515890PRTHuman papillomavirus 158Ile Tyr Thr Val Glu Leu Lys Arg Tyr Gly Gly Pro Leu Gly Ile Thr1 5 10 15Ile Ser Gly Thr Glu Glu Pro Phe Asp Pro Ile Ile Ile Ser Ser Leu 20 25 30Thr Lys Gly Gly Leu Ala Glu Arg Thr Gly Ala Ile His Ile Gly Asp 35 40 45Arg Ile Leu Ala Ile Asn Ser Ser Ser Leu Lys Gly Lys Pro Leu Ser 50 55 60Glu Ala Ile His Leu Leu Gln Met Ala Gly Glu Thr Val Thr Leu Lys65 70 75 80Ile Lys Lys Gln Thr Asp Ala Gln Ser Ala 85 9015995PRTHuman papillomavirus 159Ile Met Ser Pro Thr Pro Val Glu Leu His Lys Val Thr Leu Tyr Lys1 5 10 15Asp Ser Asp Met Glu Asp Phe Gly Phe Ser Val Ala Asp Gly Leu Leu 20 25 30Glu Lys Gly Val Tyr Val Lys Asn Ile Arg Pro Ala Gly Pro Gly Asp 35 40 45Leu Gly Gly Leu Lys Pro Tyr Asp Arg Leu Leu Gln Val Asn His Val 50 55 60Arg Thr Arg Asp Phe Asp Cys Cys Leu Val Val Pro Leu Ile Ala Glu65 70 75 80Ser Gly Asn Lys Leu Asp Leu Val Ile Ser Arg Asn Pro Leu Ala 85 90 9516088PRTHuman papillomavirus 160Ser Arg Gly Cys Glu Thr Arg Glu Leu Ala Leu Pro Arg Asp Gly Gln1 5 10 15Gly Arg Leu Gly Phe Glu Val Asp Ala Glu Gly Phe Val Thr His Val 20 25 30Glu Arg Phe Thr Phe Ala Glu Thr Ala Gly Leu Arg Pro Gly Ala Arg 35 40 45Leu Leu Arg Val Cys Gly Gln Thr Leu Pro Ser Leu Arg Pro Glu Ala 50 55 60Ala Ala Gln Leu Leu Arg Ser Ala Pro Lys Val Cys Val Thr Val Leu65 70 75 80Pro Pro Asp Glu Ser Gly Arg Pro 85161108PRTHuman papillomavirus 161Cys Ser Val Met Ile Phe Glu Val Val Glu Gln Ala Gly Ala Ile Ile1 5 10 15Leu Glu Asp Gly Gln Glu Leu Asp Ser Trp Tyr Val Ile Leu Asn Gly 20 25 30Thr Val Glu Ile Ser His Pro Asp Gly Lys Val Glu Asn Leu Phe Met 35 40 45Gly Asn Ser Phe Gly Ile Thr Pro Thr Leu Asp Lys Gln Tyr Met His 50 55 60Gly Ile Val Arg Thr Lys Val Asp Asp Cys Gln Phe Val Cys Ile Ala65 70 75 80Gln Gln Asp Tyr Trp Arg Ile Leu Asn His Val Glu Lys Asn Thr His 85 90 95Lys Val Glu Glu Glu Gly Glu Ile Val Met Val His 100 10516282PRTHuman papillomavirus 162Pro Arg Glu Thr Val Lys Ile Pro Asp Ser Ala Asp Gly Leu Gly Phe1 5 10 15Gln Ile Arg Gly Phe Gly Pro Ser Val Val His Ala Val Gly Arg Gly 20 25 30Thr Val Ala Ala Ala Ala Gly Leu His Pro Gly Gln Cys Ile Ile Lys 35 40 45Val Asn Gly Ile Asn Val Ser Lys Glu Thr His Ala Ser Val Ile Ala 50 55 60His Val Thr Ala Cys Arg Lys Tyr Arg Arg Pro Thr Lys Gln Asp Ser65 70 75 80Ile Gln16389PRTHuman papillomavirus 163Leu Glu Asn Val Ile Ala Lys Ser Leu Leu Ile Lys Ser Asn Glu Gly1 5 10 15Ser Tyr Gly Phe Gly Leu Glu Asp Lys Asn Lys Val Pro Ile Ile Lys 20 25 30Leu Val Glu Lys Gly Ser Asn Ala Glu Met Ala Gly Met Glu Val Gly 35 40 45Lys Lys Ile Phe Ala Ile Asn Gly Asp Leu Val Phe Met Arg Pro Phe 50 55 60Asn Glu Val Asp Cys Phe Leu Lys Ser Cys Leu Asn Ser Arg Lys Pro65 70 75 80Leu Arg Val Leu Val Ser Thr Lys Pro 85164100PRTHuman papillomavirus 164Glu Asp Phe Cys Tyr Val Phe Thr Val Glu Leu Glu Arg Gly Pro Ser1 5 10 15Gly Leu Gly Met Gly Leu Ile Asp Gly Met His Thr His Leu Gly Ala 20 25 30Pro Gly Leu Tyr Ile Gln Thr Leu Leu Pro Gly Ser Pro Ala Ala Ala 35 40 45Asp Gly Arg Leu Ser Leu Gly Asp Arg Ile Leu Glu Val Asn Gly Ser 50 55 60Ser Leu Leu Gly Leu Gly Tyr Leu Arg Ala Val Asp Leu Ile Arg His65 70 75 80Gly Gly Lys Lys Met Arg Phe Leu Val Ala Lys Ser Asp Val Glu Thr 85 90 95Ala Lys Lys Ile 10016591PRTHuman papillomavirus 165Ile Tyr Leu Glu Ala Phe Leu Glu Gly Gly Ala Pro Trp Gly Phe Thr1 5 10 15Leu Lys Gly Gly Leu Glu His Gly Glu Pro Leu Ile Ile Ser Lys Val 20 25 30Glu Glu Gly Gly Lys Ala Asp Thr Leu Ser Ser Lys Leu Gln Ala Gly 35 40 45Asp Glu Val Val His Ile Asn Glu Val Thr Leu Ser Ser Ser Arg Lys 50 55 60Glu Ala Val Ser Leu Val Lys Gly Ser Tyr Lys Thr Leu Arg Leu Val65 70 75 80Val Arg Arg Asp Val Cys Thr Asp Pro Gly His 85 90166100PRTHuman papillomavirus 166Asn Asn Glu Leu Thr Gln Phe Leu Pro Arg Thr Ile Thr Leu Lys Lys1 5 10 15Pro Pro Gly Ala Gln Leu Gly Phe Asn Ile Arg Gly Gly Lys Ala Ser 20 25 30Gln Leu Gly Ile Phe Ile Ser Lys Val Ile Pro Asp Ser Asp Ala His 35 40 45Arg Ala Gly Leu Gln Glu Gly Asp Gln Val Leu Ala Val Asn Asp Val 50 55 60Asp Phe Gln Asp Ile Glu His Ser Lys Ala Val Glu Ile Leu Lys Thr65 70 75 80Ala Arg Glu Ile Ser Met Arg Val Arg Phe Phe Pro Tyr Asn Tyr His 85 90 95Arg Gln Lys Glu 100167107PRTHuman papillomavirus 167Phe Leu Thr Glu Phe Gln Asp Lys Gln Ile Lys Asp Trp Lys Lys Arg1 5 10 15Phe Ile Gly Ile Arg Met Arg Thr Ile Thr Pro Ser Leu Val Asp Glu 20 25 30Leu Lys Ala Ser Asn Pro Asp Phe Pro Glu Val Ser Ser Gly Ile Tyr 35 40 45Val Gln Glu Val Ala Pro Asn Ser Pro Ser Gln Arg Gly Gly Ile Gln 50 55 60Asp Gly Asp Ile Ile Val Lys Val Asn Gly Arg Pro Leu Val Asp Ser65 70 75 80Ser Glu Leu Gln Glu Ala Val Leu Thr Glu Ser Pro Leu Leu Leu Glu 85 90 95Val Arg Arg Gly Asn Asp Asp Leu Leu Phe Ser 100 10516894PRTHuman papillomavirus 168Asn Lys Lys Tyr Leu Gly Leu Gln Met Leu Ser Leu Thr Val Pro Leu1 5 10 15Ser Glu Glu Leu Lys Met His Tyr Pro Asp Phe Pro Asp Val Ser Ser 20 25 30Gly Val Tyr Val Cys Lys Val Val Glu Gly Thr Ala Ala Gln Ser Ser 35 40 45Gly Leu Arg Asp His Asp Val Ile Val Asn Ile Asn Gly Lys Pro Ile 50 55 60Thr Thr Thr Thr Asp Val Val Lys Ala Leu Asp Ser Asp Ser Leu Ser65 70 75 80Met Ala Val Leu Arg Gly Lys Asp Asn Leu Leu Leu Thr Val 85 90169111PRTHuman papillomavirus 169Pro Gly Ser Asp Ser Ser Leu Phe Glu Thr Tyr Asn Val Glu Leu Val1 5 10 15Arg Lys Asp Gly Gln Ser Leu Gly Ile Arg Ile Val Gly Tyr Val Gly 20 25 30Thr Ser His Thr Gly Glu Ala Ser Gly Ile Tyr Val Lys Ser Ile Ile 35 40 45Pro Gly Ser Ala Ala Tyr His Asn Gly His Ile Gln Val Asn Asp Lys 50 55 60Ile Val Ala Val Asp Gly Val Asn Ile Gln Gly Phe Ala Asn His Asp65 70 75 80Val Val Glu Val Leu Arg Asn Ala Gly Gln Val Val His Leu Thr Leu 85 90 95Val Arg Arg Lys Thr Ser Ser Ser Thr Ser Arg Ile His Arg Asp 100 105 11017093PRTHuman papillomavirus 170Pro Ala Thr Cys Pro Ile Val Pro Gly Gln Glu Met Ile Ile Glu Ile1 5 10 15Ser Lys Gly Arg Ser Gly Leu Gly Leu Ser Ile Val Gly Gly Lys Asp 20 25 30Thr Pro Leu Asn Ala Ile Val Ile His Glu Val Tyr Glu Glu Gly Ala 35 40 45Ala Ala Arg Asp Gly Arg Leu Trp Ala Gly Asp Gln Ile Leu Glu Val 50 55 60Asn Gly Val Asp Leu Arg Asn Ser Ser His Glu Glu Ala Ile Thr Ala65 70 75 80Leu Arg Gln Thr Pro Gln Lys Val Arg Leu Val Val Tyr 85 90171100PRTHuman papillomavirus 171Leu Pro Glu Thr Val Cys Trp Gly His Val Glu Glu Val Glu Leu Ile1 5 10 15Asn Asp Gly Ser Gly Leu Gly Phe Gly Ile Val Gly Gly Lys Thr Ser 20 25 30Gly Val Val Val Arg Thr Ile Val Pro Gly Gly Leu Ala Asp Arg Asp 35 40 45Gly Arg Leu Gln Thr Gly Asp His Ile Leu Lys Ile Gly Gly Thr Asn 50 55 60Val Gln Gly Met Thr Ser Glu Gln Val Ala Gln Val Leu Arg Asn Cys65 70 75 80Gly Asn Ser Val Arg Met Leu Val Ala Arg Asp Pro Ala Gly Asp Ile 85 90 95Gln Ser Pro Ile 100172119PRTHuman papillomavirus 172Pro Asn Phe Ser His Trp Gly Pro Pro Arg Ile Val Glu Ile Phe Arg1 5 10 15Glu Pro Asn Val Ser Leu Gly Ile Ser Ile Val Val Gly Gln Thr Val 20 25 30Ile Lys Arg Leu Lys Asn Gly Glu Glu Leu Lys Gly Ile Phe Ile Lys 35 40 45Gln Val Leu Glu Asp Ser Pro Ala Gly Lys Thr Asn Ala Leu Lys Thr 50 55 60Gly Asp Lys Ile Leu Glu Val Ser Gly Val Asp Leu Gln Asn Ala Ser65 70 75 80His Ser Glu Ala Val Glu Ala Ile Lys Asn Ala Gly Asn Pro Val Val 85 90 95Phe Ile Val Gln Ser Leu Ser Ser Thr Pro Arg Val Ile Pro Asn Val 100 105 110His Asn Lys Ala Asn Ser Ser 11517399PRTHuman papillomavirus 173Pro Gly Glu Leu His Ile Ile Glu Leu Glu Lys Asp Lys Asn Gly Leu1 5 10 15Gly Leu Ser Leu Ala Gly Asn Lys Asp Arg Ser Arg Met Ser Ile Phe 20 25

30Val Val Gly Ile Asn Pro Glu Gly Pro Ala Ala Ala Asp Gly Arg Met 35 40 45Arg Ile Gly Asp Glu Leu Leu Glu Ile Asn Asn Gln Ile Leu Tyr Gly 50 55 60Arg Ser His Gln Asn Ala Ser Ala Ile Ile Lys Thr Ala Pro Ser Lys65 70 75 80Val Lys Leu Val Phe Ile Arg Asn Glu Asp Ala Val Asn Gln Met Ala 85 90 95Asn Ser Ser174102PRTHuman papillomavirus 174Leu Ser Ser Pro Glu Val Lys Ile Val Glu Leu Val Lys Asp Cys Lys1 5 10 15Gly Leu Gly Phe Ser Ile Leu Asp Tyr Gln Asp Pro Leu Asp Pro Thr 20 25 30Arg Ser Val Ile Val Ile Arg Ser Leu Val Ala Asp Gly Val Ala Glu 35 40 45Arg Ser Gly Gly Leu Leu Pro Gly Asp Arg Leu Val Ser Val Asn Glu 50 55 60Tyr Cys Leu Asp Asn Thr Ser Leu Ala Glu Ala Val Glu Ile Leu Lys65 70 75 80Ala Val Pro Pro Gly Leu Val His Leu Gly Ile Cys Lys Pro Leu Val 85 90 95Glu Phe Ile Val Thr Asp 100175104PRTHuman papillomavirus 175Ile Trp Gln Ile Glu Tyr Ile Asp Ile Glu Arg Pro Ser Thr Gly Gly1 5 10 15Leu Gly Phe Ser Val Val Ala Leu Arg Ser Gln Asn Leu Gly Lys Val 20 25 30Asp Ile Phe Val Lys Asp Val Gln Pro Gly Ser Val Ala Asp Arg Asp 35 40 45Gln Arg Leu Lys Glu Asn Asp Gln Ile Leu Ala Ile Asn His Thr Pro 50 55 60Leu Asp Gln Asn Ile Ser His Gln Gln Ala Ile Ala Leu Leu Gln Gln65 70 75 80Thr Thr Gly Ser Leu Arg Leu Ile Val Ala Arg Glu Pro Val His Thr 85 90 95Lys Ser Ser Thr Ser Ser Ser Glu 10017696PRTHuman papillomavirus 176Asn Ser Asp Asp Ala Glu Leu Gln Lys Tyr Ser Lys Leu Leu Pro Ile1 5 10 15His Thr Leu Arg Leu Gly Val Glu Val Asp Ser Phe Asp Gly His His 20 25 30Tyr Ile Ser Ser Ile Val Ser Gly Gly Pro Val Asp Thr Leu Gly Leu 35 40 45Leu Gln Pro Glu Asp Glu Leu Leu Glu Val Asn Gly Met Gln Leu Tyr 50 55 60Gly Lys Ser Arg Arg Glu Ala Val Ser Phe Leu Lys Glu Val Pro Pro65 70 75 80Pro Phe Thr Leu Val Cys Cys Arg Arg Leu Phe Asp Asp Glu Ala Ser 85 90 95177118PRTHuman papillomavirus 177His Leu Arg Leu Leu Asn Ile Ala Cys Ala Ala Lys Ala Lys Arg Arg1 5 10 15Leu Met Thr Leu Thr Lys Pro Ser Arg Glu Ala Pro Leu Pro Phe Ile 20 25 30Leu Leu Gly Gly Ser Glu Lys Gly Phe Gly Ile Phe Val Asp Ser Val 35 40 45Asp Ser Gly Ser Lys Ala Thr Glu Ala Gly Leu Lys Arg Gly Asp Gln 50 55 60Ile Leu Glu Val Asn Gly Gln Asn Phe Glu Asn Ile Gln Leu Ser Lys65 70 75 80Ala Met Glu Ile Leu Arg Asn Asn Thr His Leu Ser Ile Thr Val Lys 85 90 95Thr Asn Leu Phe Val Phe Lys Glu Leu Leu Thr Arg Leu Ser Glu Glu 100 105 110Lys Arg Asn Gly Ala Pro 11517888PRTHuman papillomavirus 178Ile Pro Pro Ala Pro Arg Lys Val Glu Met Arg Arg Asp Pro Val Leu1 5 10 15Gly Phe Gly Phe Val Ala Gly Ser Glu Lys Pro Val Val Val Arg Ser 20 25 30Val Thr Pro Gly Gly Pro Ser Glu Gly Lys Leu Ile Pro Gly Asp Gln 35 40 45Ile Val Met Ile Asn Asp Glu Pro Val Ser Ala Ala Pro Arg Glu Arg 50 55 60Val Ile Asp Leu Val Arg Ser Cys Lys Glu Ser Ile Leu Leu Thr Val65 70 75 80Ile Gln Pro Tyr Pro Ser Pro Lys 85179101PRTHuman papillomavirus 179Leu Asn Lys Arg Thr Thr Met Pro Lys Asp Ser Gly Ala Leu Leu Gly1 5 10 15Leu Lys Val Val Gly Gly Lys Met Thr Asp Leu Gly Arg Leu Gly Ala 20 25 30Phe Ile Thr Lys Val Lys Lys Gly Ser Leu Ala Asp Val Val Gly His 35 40 45Leu Arg Ala Gly Asp Glu Val Leu Glu Trp Asn Gly Lys Pro Leu Pro 50 55 60Gly Ala Thr Asn Glu Glu Val Tyr Asn Ile Ile Leu Glu Ser Lys Ser65 70 75 80Glu Pro Gln Val Glu Ile Ile Val Ser Arg Pro Ile Gly Asp Ile Pro 85 90 95Arg Ile His Arg Asp 10018077PRTHuman papillomavirus 180Arg Cys Val Ile Ile Gln Lys Asp Gln His Gly Phe Gly Phe Thr Val1 5 10 15Ser Gly Asp Arg Ile Val Leu Val Gln Ser Val Arg Pro Gly Gly Ala 20 25 30Ala Met Lys Ala Gly Val Lys Glu Gly Asp Arg Ile Ile Lys Val Asn 35 40 45Gly Thr Met Val Thr Asn Ser Ser His Leu Glu Val Val Lys Leu Ile 50 55 60Lys Ser Gly Ala Tyr Val Ala Leu Thr Leu Leu Gly Ser65 70 7518187PRTHuman papillomavirus 181Ile Leu Val Gln Arg Cys Val Ile Ile Gln Lys Asp Asp Asn Gly Phe1 5 10 15Gly Leu Thr Val Ser Gly Asp Asn Pro Val Phe Val Gln Ser Val Lys 20 25 30Glu Asp Gly Ala Ala Met Arg Ala Gly Val Gln Thr Gly Asp Arg Ile 35 40 45Ile Lys Val Asn Gly Thr Leu Val Thr His Ser Asn His Leu Glu Val 50 55 60Val Lys Leu Ile Lys Ser Gly Ser Tyr Val Ala Leu Thr Val Gln Gly65 70 75 80Arg Pro Pro Gly Asn Ser Ser 8518278PRTHuman papillomavirus 182Ser Val Glu Met Thr Leu Arg Arg Asn Gly Leu Gly Gln Leu Gly Phe1 5 10 15His Val Asn Tyr Glu Gly Ile Val Ala Asp Val Glu Pro Tyr Gly Tyr 20 25 30Ala Trp Gln Ala Gly Leu Arg Gln Gly Ser Arg Leu Val Glu Ile Cys 35 40 45Lys Val Ala Val Ala Thr Leu Ser His Glu Gln Met Ile Asp Leu Leu 50 55 60Arg Thr Ser Val Thr Val Lys Val Val Ile Ile Pro Pro His65 70 7518396PRTHuman papillomavirus 183Leu Lys Val Met Thr Ser Gly Trp Glu Thr Val Asp Met Thr Leu Arg1 5 10 15Arg Asn Gly Leu Gly Gln Leu Gly Phe His Val Lys Tyr Asp Gly Thr 20 25 30Val Ala Glu Val Glu Asp Tyr Gly Phe Ala Trp Gln Ala Gly Leu Arg 35 40 45Gln Gly Ser Arg Leu Val Glu Ile Cys Lys Val Ala Val Val Thr Leu 50 55 60Thr His Asp Gln Met Ile Asp Leu Leu Arg Thr Ser Val Thr Val Lys65 70 75 80Val Val Ile Ile Pro Pro Phe Glu Asp Gly Thr Pro Arg Arg Gly Trp 85 90 95184105PRTHuman papillomavirus 184His Tyr Ile Phe Pro His Ala Arg Ile Lys Ile Thr Arg Asp Ser Lys1 5 10 15Asp His Thr Val Ser Gly Asn Gly Leu Gly Ile Arg Ile Val Gly Gly 20 25 30Lys Glu Ile Pro Gly His Ser Gly Glu Ile Gly Ala Tyr Ile Ala Lys 35 40 45Ile Leu Pro Gly Gly Ser Ala Glu Gln Thr Gly Lys Leu Met Glu Gly 50 55 60Met Gln Val Leu Glu Trp Asn Gly Ile Pro Leu Thr Ser Lys Thr Tyr65 70 75 80Glu Glu Val Gln Ser Ile Ile Ser Gln Gln Ser Gly Glu Ala Glu Ile 85 90 95Cys Val Arg Leu Asp Leu Asn Met Leu 100 10518586PRTHuman papillomavirus 185Ser Tyr Ser Val Thr Leu Thr Gly Pro Gly Pro Trp Gly Phe Arg Leu1 5 10 15Gln Gly Gly Lys Asp Phe Asn Met Pro Leu Thr Ile Ser Arg Ile Thr 20 25 30Pro Gly Ser Lys Ala Ala Gln Ser Gln Leu Ser Gln Gly Asp Leu Val 35 40 45Val Ala Ile Asp Gly Val Asn Thr Asp Thr Met Thr His Leu Glu Ala 50 55 60Gln Asn Lys Ile Lys Ser Ala Ser Tyr Asn Leu Ser Leu Thr Leu Gln65 70 75 80Lys Ser Lys Asn Ser Ser 8518694PRTHuman papillomavirus 186Phe Ser Asp Met Arg Ile Ser Ile Asn Gln Thr Pro Gly Lys Ser Leu1 5 10 15Asp Phe Gly Phe Thr Ile Lys Trp Asp Ile Pro Gly Ile Phe Val Ala 20 25 30Ser Val Glu Ala Gly Ser Pro Ala Glu Phe Ser Gln Leu Gln Val Asp 35 40 45Asp Glu Ile Ile Ala Ile Asn Asn Thr Lys Phe Ser Tyr Asn Asp Ser 50 55 60Lys Glu Trp Glu Glu Ala Met Ala Lys Ala Gln Glu Thr Gly His Leu65 70 75 80Val Met Asp Val Arg Arg Tyr Gly Lys Ala Gly Ser Pro Glu 85 9018798PRTHuman papillomavirus 187Gln Ser Ala His Leu Glu Val Ile Gln Leu Ala Asn Ile Lys Pro Ser1 5 10 15Glu Gly Leu Gly Met Tyr Ile Lys Ser Thr Tyr Asp Gly Leu His Val 20 25 30Ile Thr Gly Thr Thr Glu Asn Ser Pro Ala Asp Arg Cys Lys Lys Ile 35 40 45His Ala Gly Asp Glu Val Ile Gln Val Asn His Gln Thr Val Val Gly 50 55 60Trp Gln Leu Lys Asn Leu Val Asn Ala Leu Arg Glu Asp Pro Ser Gly65 70 75 80Val Ile Leu Thr Leu Lys Lys Arg Pro Gln Ser Met Leu Thr Ser Ala 85 90 95Pro Ala188100PRTHuman papillomavirus 188Ile Leu Thr Gln Thr Leu Ile Pro Val Arg His Thr Val Lys Ile Asp1 5 10 15Lys Asp Thr Leu Leu Gln Asp Tyr Gly Phe His Ile Ser Glu Ser Leu 20 25 30Pro Leu Thr Val Val Ala Val Thr Ala Gly Gly Ser Ala His Gly Lys 35 40 45Leu Phe Pro Gly Asp Gln Ile Leu Gln Met Asn Asn Glu Pro Ala Glu 50 55 60Asp Leu Ser Trp Glu Arg Ala Val Asp Ile Leu Arg Glu Ala Glu Asp65 70 75 80Ser Leu Ser Ile Thr Val Val Arg Cys Thr Ser Gly Val Pro Lys Ser 85 90 95Ser Asn Ser Ser 10018991PRTHuman papillomavirus 189Arg Ser Phe Gln Tyr Val Pro Val Gln Leu Gln Gly Gly Ala Pro Trp1 5 10 15Gly Phe Thr Leu Lys Gly Gly Leu Glu His Cys Glu Pro Leu Thr Val 20 25 30Ser Lys Ile Glu Asp Gly Gly Lys Ala Ala Leu Ser Gln Lys Met Arg 35 40 45Thr Gly Asp Glu Leu Val Asn Ile Asn Gly Thr Pro Leu Tyr Gly Ser 50 55 60Arg Gln Glu Ala Leu Ile Leu Ile Lys Gly Ser Phe Arg Ile Leu Lys65 70 75 80Leu Ile Val Arg Arg Arg Asn Ala Pro Val Ser 85 90190103PRTHuman papillomavirus 190Ile Leu Glu Lys Leu Glu Leu Phe Pro Val Glu Leu Glu Lys Asp Glu1 5 10 15Asp Gly Leu Gly Ile Ser Ile Ile Gly Met Gly Val Gly Ala Asp Ala 20 25 30Gly Leu Glu Lys Leu Gly Ile Phe Val Lys Thr Val Thr Glu Gly Gly 35 40 45Ala Ala Gln Arg Asp Gly Arg Ile Gln Val Asn Asp Gln Ile Val Glu 50 55 60Val Asp Gly Ile Ser Leu Val Gly Val Thr Gln Asn Phe Ala Ala Thr65 70 75 80Val Leu Arg Asn Thr Lys Gly Asn Val Arg Phe Val Ile Gly Arg Glu 85 90 95Lys Pro Gly Gln Val Ser Glu 100191113PRTHuman papillomavirus 191Lys Asp Val Asn Val Tyr Val Asn Pro Lys Lys Leu Thr Val Ile Lys1 5 10 15Ala Lys Glu Gln Leu Lys Leu Leu Glu Val Leu Val Gly Ile Ile His 20 25 30Gln Thr Lys Trp Ser Trp Arg Arg Thr Gly Lys Gln Gly Asp Gly Glu 35 40 45Arg Leu Val Val His Gly Leu Leu Pro Gly Gly Ser Ala Met Lys Ser 50 55 60Gly Gln Val Leu Ile Gly Asp Val Leu Val Ala Val Asn Asp Val Asp65 70 75 80Val Thr Thr Glu Asn Ile Glu Arg Val Leu Ser Cys Ile Pro Gly Pro 85 90 95Met Gln Val Lys Leu Thr Phe Glu Asn Ala Tyr Asp Val Lys Arg Glu 100 105 110Thr19290PRTHuman papillomavirus 192Thr Arg Gly Cys Glu Thr Val Glu Met Thr Leu Arg Arg Asn Gly Leu1 5 10 15Gly Gln Leu Gly Phe His Val Asn Phe Glu Gly Ile Val Ala Asp Val 20 25 30Glu Pro Phe Gly Phe Ala Trp Lys Ala Gly Leu Arg Gln Gly Ser Arg 35 40 45Leu Val Glu Ile Cys Lys Val Ala Val Ala Thr Leu Thr His Glu Gln 50 55 60Met Ile Asp Leu Leu Arg Thr Ser Val Thr Val Lys Val Val Ile Ile65 70 75 80Gln Pro His Asp Asp Gly Ser Pro Arg Arg 85 9019396PRTHuman papillomavirus 193Val Glu Asn Ile Leu Ala Lys Arg Leu Leu Ile Leu Pro Gln Glu Glu1 5 10 15Asp Tyr Gly Phe Asp Ile Glu Glu Lys Asn Lys Ala Val Val Val Lys 20 25 30Ser Val Gln Arg Gly Ser Leu Ala Glu Val Ala Gly Leu Gln Val Gly 35 40 45Arg Lys Ile Tyr Ser Ile Asn Glu Asp Leu Val Phe Leu Arg Pro Phe 50 55 60Ser Glu Val Glu Ser Ile Leu Asn Gln Ser Phe Cys Ser Arg Arg Pro65 70 75 80Leu Arg Leu Leu Val Ala Thr Lys Ala Lys Glu Ile Ile Lys Ile Pro 85 90 95194103PRTHuman papillomavirus 194Pro Asp Ser Ala Gly Pro Gly Glu Val Arg Leu Val Ser Leu Arg Arg1 5 10 15Ala Lys Ala His Glu Gly Leu Gly Phe Ser Ile Arg Gly Gly Ser Glu 20 25 30His Gly Val Gly Ile Tyr Val Ser Leu Val Glu Pro Gly Ser Leu Ala 35 40 45Glu Lys Glu Gly Leu Arg Val Gly Asp Gln Ile Leu Arg Val Asn Asp 50 55 60Lys Ser Leu Ala Arg Val Thr His Ala Glu Ala Val Lys Ala Leu Lys65 70 75 80Gly Ser Lys Lys Leu Val Leu Ser Val Tyr Ser Ala Gly Arg Ile Pro 85 90 95Gly Gly Tyr Val Thr Asn His 100195100PRTHuman papillomavirus 195Leu Gln Gly Gly Asp Glu Lys Lys Val Asn Leu Val Leu Gly Asp Gly1 5 10 15Arg Ser Leu Gly Leu Thr Ile Arg Gly Gly Ala Glu Tyr Gly Leu Gly 20 25 30Ile Tyr Ile Thr Gly Val Asp Pro Gly Ser Glu Ala Glu Gly Ser Gly 35 40 45Leu Lys Val Gly Asp Gln Ile Leu Glu Val Asn Gly Arg Ser Phe Leu 50 55 60Asn Ile Leu His Asp Glu Ala Val Arg Leu Leu Lys Ser Ser Arg His65 70 75 80Leu Ile Leu Thr Val Lys Asp Val Gly Arg Leu Pro His Ala Arg Thr 85 90 95Thr Val Asp Glu 10019698PRTHuman papillomavirus 196Leu Arg Arg Ala Glu Leu Val Glu Ile Ile Val Glu Thr Glu Ala Gln1 5 10 15Thr Gly Val Ser Gly Ile Asn Val Ala Gly Gly Gly Lys Glu Gly Ile 20 25 30Phe Val Arg Glu Leu Arg Glu Asp Ser Pro Ala Ala Arg Ser Leu Ser 35 40 45Leu Gln Glu Gly Asp Gln Leu Leu Ser Ala Arg Val Phe Phe Glu Asn 50 55 60Phe Lys Tyr Glu Asp Ala Leu Arg Leu Leu Gln Cys Ala Glu Pro Tyr65 70 75 80Lys Val Ser Phe Cys Leu Lys Arg Thr Val Pro Thr Gly Asp Leu Ala 85 90 95Leu Arg19794PRTHuman papillomavirus 197Ile Gln Thr Thr Gly Ala Val Ser Tyr Thr Val Glu Leu Lys Arg Tyr1 5 10 15Gly Gly Pro Leu Gly Ile Thr Ile Ser Gly Thr Glu Glu Pro Phe Asp 20 25 30Pro Ile Val Ile Ser Gly Leu Thr Lys Arg Gly Leu Ala Glu Arg Thr 35 40 45Gly Ala Ile His Val Gly Asp Arg Ile Leu Ala Ile Asn Asn Val Ser 50 55 60Leu Lys Gly Arg Pro Leu Ser Glu Ala Ile His Leu Leu Gln Val Ala65 70 75 80Gly Glu Thr Val Thr Leu Lys Ile Lys Lys Gln Leu Asp Arg 85 90198105PRTHuman papillomavirus 198Ile Leu Glu Met Glu Glu Leu Leu Leu Pro Thr Pro Leu Glu Met His1 5 10

15Lys Val Thr Leu His Lys Asp Pro Met Arg His Asp Phe Gly Phe Ser 20 25 30Val Ser Asp Gly Leu Leu Glu Lys Gly Val Tyr Val His Thr Val Arg 35 40 45Pro Asp Gly Pro Ala His Arg Gly Gly Leu Gln Pro Phe Asp Arg Val 50 55 60Leu Gln Val Asn His Val Arg Thr Arg Asp Phe Asp Cys Cys Leu Ala65 70 75 80Val Pro Leu Leu Ala Glu Ala Gly Asp Val Leu Glu Leu Ile Ile Ser 85 90 95Arg Lys Pro His Thr Ala His Ser Ser 100 105199102PRTHuman papillomavirus 199Ile His Thr Val Ala Asn Ala Ser Gly Pro Leu Met Val Glu Ile Val1 5 10 15Lys Thr Pro Gly Ser Ala Leu Gly Ile Ser Leu Thr Thr Thr Ser Leu 20 25 30Arg Asn Lys Ser Val Ile Thr Ile Asp Arg Ile Lys Pro Ala Ser Val 35 40 45Val Asp Arg Ser Gly Ala Leu His Pro Gly Asp His Ile Leu Ser Ile 50 55 60Asp Gly Thr Ser Met Glu His Cys Ser Leu Leu Glu Ala Thr Lys Leu65 70 75 80Leu Ala Ser Ile Ser Glu Lys Val Arg Leu Glu Ile Leu Pro Val Pro 85 90 95Gln Ser Gln Arg Pro Leu 10020084PRTHuman papillomavirus 200Ile Thr Val Val Glu Leu Ile Lys Lys Glu Gly Ser Thr Leu Gly Leu1 5 10 15Thr Ile Ser Gly Gly Thr Asp Lys Asp Gly Lys Pro Arg Val Ser Asn 20 25 30Leu Arg Pro Gly Gly Leu Ala Ala Arg Ser Asp Leu Leu Asn Ile Gly 35 40 45Asp Tyr Ile Arg Ser Val Asn Gly Ile His Leu Thr Arg Leu Arg His 50 55 60Asp Glu Ile Ile Thr Leu Leu Lys Asn Val Gly Glu Arg Val Val Leu65 70 75 80Glu Val Glu Tyr201103PRTHuman papillomavirus 201Ile Gln Ile Val His Thr Glu Thr Thr Glu Val Val Leu Cys Gly Asp1 5 10 15Pro Leu Ser Gly Phe Gly Leu Gln Leu Gln Gly Gly Ile Phe Ala Thr 20 25 30Glu Thr Leu Ser Ser Pro Pro Leu Val Cys Phe Ile Glu Pro Asp Ser 35 40 45Pro Ala Glu Arg Cys Gly Leu Leu Gln Val Gly Asp Arg Val Leu Ser 50 55 60Ile Asn Gly Ile Ala Thr Glu Asp Gly Thr Met Glu Glu Ala Asn Gln65 70 75 80Leu Leu Arg Asp Ala Ala Leu Ala His Lys Val Val Leu Glu Val Glu 85 90 95Phe Asp Val Ala Glu Ser Val 10020292PRTHuman papillomavirus 202Ile Leu Asp Val Ser Leu Tyr Lys Glu Gly Asn Ser Phe Gly Phe Val1 5 10 15Leu Arg Gly Gly Ala His Glu Asp Gly His Lys Ser Arg Pro Leu Val 20 25 30Leu Thr Tyr Val Arg Pro Gly Gly Pro Ala Asp Arg Glu Gly Ser Leu 35 40 45Lys Val Gly Asp Arg Leu Leu Ser Val Asp Gly Ile Pro Leu His Gly 50 55 60Ala Ser His Ala Thr Ala Leu Ala Thr Leu Arg Gln Cys Ser His Glu65 70 75 80Ala Leu Phe Gln Val Glu Tyr Asp Val Ala Thr Pro 85 90203102PRTHuman papillomavirus 203Gln Phe Asp Val Ala Glu Ser Val Ile Pro Ser Ser Gly Thr Phe His1 5 10 15Val Lys Leu Pro Lys Lys Arg Ser Val Glu Leu Gly Ile Thr Ile Ser 20 25 30Ser Ala Ser Arg Lys Arg Gly Glu Pro Leu Ile Ile Ser Asp Ile Lys 35 40 45Lys Gly Ser Val Ala His Arg Thr Gly Thr Leu Glu Pro Gly Asp Lys 50 55 60Leu Leu Ala Ile Asp Asn Ile Arg Leu Asp Asn Cys Pro Met Glu Asp65 70 75 80Ala Val Gln Ile Leu Arg Gln Cys Glu Asp Leu Val Lys Leu Lys Ile 85 90 95Arg Lys Asp Glu Asp Asn 10020491PRTHuman papillomavirus 204Met Ala Leu Thr Val Asp Val Ala Gly Pro Ala Pro Trp Gly Phe Arg1 5 10 15Ile Thr Gly Gly Arg Asp Phe His Thr Pro Ile Met Val Thr Lys Val 20 25 30Ala Glu Arg Gly Lys Ala Lys Asp Ala Asp Leu Arg Pro Gly Asp Ile 35 40 45Ile Val Ala Ile Asn Gly Glu Ser Ala Glu Gly Met Leu His Ala Glu 50 55 60Ala Gln Ser Lys Ile Arg Gln Ser Pro Ser Pro Leu Arg Leu Gln Leu65 70 75 80Asp Arg Ser Gln Ala Thr Ser Pro Gly Gln Thr 85 9020584PRTHuman papillomavirus 205Ser Asn Tyr Ser Val Ser Leu Val Gly Pro Ala Pro Trp Gly Phe Arg1 5 10 15Leu Gln Gly Gly Lys Asp Phe Asn Met Pro Leu Thr Ile Ser Ser Leu 20 25 30Lys Asp Gly Gly Lys Ala Ala Gln Ala Asn Val Arg Ile Gly Asp Val 35 40 45Val Leu Ser Ile Asp Gly Ile Asn Ala Gln Gly Met Thr His Leu Glu 50 55 60Ala Gln Asn Lys Ile Lys Gly Cys Thr Gly Ser Leu Asn Met Thr Leu65 70 75 80Gln Arg Ala Ser206133PRTHuman papillomavirus 206Thr Leu Val Glu His Ser Lys Leu Tyr Cys Gly His Cys Tyr Tyr Gln1 5 10 15Thr Val Val Thr Pro Val Ile Glu Gln Ile Leu Pro Asp Ser Pro Gly 20 25 30Ser His Leu Pro His Thr Val Thr Leu Val Ser Ile Pro Ala Ser Ser 35 40 45His Gly Lys Arg Gly Leu Ser Val Ser Ile Asp Pro Pro His Gly Pro 50 55 60Pro Gly Cys Gly Thr Glu His Ser His Thr Val Arg Val Gln Gly Val65 70 75 80Asp Pro Gly Cys Met Ser Pro Asp Val Lys Asn Ser Ile His Val Gly 85 90 95Asp Arg Ile Leu Glu Ile Asn Gly Thr Pro Ile Arg Asn Val Pro Leu 100 105 110Asp Glu Ile Asp Leu Leu Ile Gln Glu Thr Ser Arg Leu Leu Gln Leu 115 120 125Thr Leu Glu His Asp 13020792PRTHuman papillomavirus 207Pro Tyr Ser Val Thr Leu Ile Ser Met Pro Ala Thr Thr Glu Gly Arg1 5 10 15Arg Gly Phe Ser Val Ser Val Glu Ser Ala Cys Ser Asn Tyr Ala Thr 20 25 30Thr Val Gln Val Lys Glu Val Asn Arg Met His Ile Ser Pro Asn Asn 35 40 45Arg Asn Ala Ile His Pro Gly Asp Arg Ile Leu Glu Ile Asn Gly Thr 50 55 60Pro Val Arg Thr Leu Arg Val Glu Glu Val Glu Asp Ala Ile Ser Gln65 70 75 80Thr Ser Gln Thr Leu Gln Leu Leu Ile Glu His Asp 85 9020882PRTHuman papillomavirus 208Ile His Ser Val Thr Leu Arg Gly Pro Ser Pro Trp Gly Phe Arg Leu1 5 10 15Val Gly Arg Asp Phe Ser Ala Pro Leu Thr Ile Ser Arg Val His Ala 20 25 30Gly Ser Lys Ala Ser Leu Ala Ala Leu Cys Pro Gly Asp Leu Ile Gln 35 40 45Ala Ile Asn Gly Glu Ser Thr Glu Leu Met Thr His Leu Glu Ala Gln 50 55 60Asn Arg Ile Lys Gly Cys His Asp His Leu Thr Leu Ser Val Ser Arg65 70 75 80Pro Glu20974PRTHuman papillomavirus 209Val Cys Tyr Arg Thr Asp Asp Glu Glu Asp Leu Gly Ile Tyr Val Gly1 5 10 15Glu Val Asn Pro Asn Ser Ile Ala Ala Lys Asp Gly Arg Ile Arg Glu 20 25 30Gly Asp Arg Ile Ile Gln Ile Asn Gly Val Asp Val Gln Asn Arg Glu 35 40 45Glu Ala Val Ala Ile Leu Ser Gln Glu Glu Asn Thr Asn Ile Ser Leu 50 55 60Leu Val Ala Arg Pro Glu Ser Gln Leu Ala65 7021093PRTHuman papillomavirus 210Ile Pro Ala Thr Gln Pro Glu Leu Ile Thr Val His Ile Val Lys Gly1 5 10 15Pro Met Gly Phe Gly Phe Thr Ile Ala Asp Ser Pro Gly Gly Gly Gly 20 25 30Gln Arg Val Lys Gln Ile Val Asp Ser Pro Arg Cys Arg Gly Leu Lys 35 40 45Glu Gly Asp Leu Ile Val Glu Val Asn Lys Lys Asn Val Gln Ala Leu 50 55 60Thr His Asn Gln Val Val Asp Met Leu Val Glu Cys Pro Lys Gly Ser65 70 75 80Glu Val Thr Leu Leu Val Gln Arg Gly Gly Asn Ser Ser 85 90211103PRTHuman papillomavirus 211Ile Pro Asp Tyr Gln Glu Gln Asp Ile Phe Leu Trp Arg Lys Glu Thr1 5 10 15Gly Phe Gly Phe Arg Ile Leu Gly Gly Asn Glu Pro Gly Glu Pro Ile 20 25 30Tyr Ile Gly His Ile Val Pro Leu Gly Ala Ala Asp Thr Asp Gly Arg 35 40 45Leu Arg Ser Gly Asp Glu Leu Ile Cys Val Asp Gly Thr Pro Val Ile 50 55 60Gly Lys Ser His Gln Leu Val Val Gln Leu Met Gln Gln Ala Ala Lys65 70 75 80Gln Gly His Val Asn Leu Thr Val Arg Arg Lys Val Val Phe Ala Val 85 90 95Pro Lys Thr Glu Asn Ser Ser 100212120PRTHuman papillomavirus 212Ile Pro Gly Val Val Ser Thr Val Val Gln Pro Tyr Asp Val Glu Ile1 5 10 15Arg Arg Gly Glu Asn Glu Gly Phe Gly Phe Val Ile Val Ser Ser Val 20 25 30Ser Arg Pro Glu Ala Gly Thr Thr Phe Ala Gly Asn Ala Cys Val Ala 35 40 45Met Pro His Lys Ile Gly Arg Ile Ile Glu Gly Ser Pro Ala Asp Arg 50 55 60Cys Gly Lys Leu Lys Val Gly Asp Arg Ile Leu Ala Val Asn Gly Cys65 70 75 80Ser Ile Thr Asn Lys Ser His Ser Asp Ile Val Asn Leu Ile Lys Glu 85 90 95Ala Gly Asn Thr Val Thr Leu Arg Ile Ile Pro Gly Asp Glu Ser Ser 100 105 110Asn Ala Glu Phe Ile Val Thr Asp 115 120213107PRTHuman papillomavirus 213Ile Pro Ser Glu Leu Lys Gly Lys Phe Ile His Thr Lys Leu Arg Lys1 5 10 15Ser Ser Arg Gly Phe Gly Phe Thr Val Val Gly Gly Asp Glu Pro Asp 20 25 30Glu Phe Leu Gln Ile Lys Ser Leu Val Leu Asp Gly Pro Ala Ala Leu 35 40 45Asp Gly Lys Met Glu Thr Gly Asp Val Ile Val Ser Val Asn Asp Thr 50 55 60Cys Val Leu Gly His Thr His Ala Gln Val Val Lys Ile Phe Gln Ser65 70 75 80Ile Pro Ile Gly Ala Ser Val Asp Leu Glu Leu Cys Arg Gly Tyr Pro 85 90 95Leu Pro Phe Asp Pro Asp Gly Ile His Arg Asp 100 10521491PRTHuman papillomavirus 214Gln Ala Thr Gln Glu Gln Asp Phe Tyr Thr Val Glu Leu Glu Arg Gly1 5 10 15Ala Lys Gly Phe Gly Phe Ser Leu Arg Gly Gly Arg Glu Tyr Asn Met 20 25 30Asp Leu Tyr Val Leu Arg Leu Ala Glu Asp Gly Pro Ala Glu Arg Cys 35 40 45Gly Lys Met Arg Ile Gly Asp Glu Ile Leu Glu Ile Asn Gly Glu Thr 50 55 60Thr Lys Asn Met Lys His Ser Arg Ala Ile Glu Leu Ile Lys Asn Gly65 70 75 80Gly Arg Arg Val Arg Leu Phe Leu Lys Arg Gly 85 90215104PRTHuman papillomavirus 215Arg Glu Lys Pro Leu Phe Thr Arg Asp Ala Ser Gln Leu Lys Gly Thr1 5 10 15Phe Leu Ser Thr Thr Leu Lys Lys Ser Asn Met Gly Phe Gly Phe Thr 20 25 30Ile Ile Gly Gly Asp Glu Pro Asp Glu Phe Leu Gln Val Lys Ser Val 35 40 45Ile Pro Asp Gly Pro Ala Ala Gln Asp Gly Lys Met Glu Thr Gly Asp 50 55 60Val Ile Val Tyr Ile Asn Glu Val Cys Val Leu Gly His Thr His Ala65 70 75 80Asp Val Val Lys Leu Phe Gln Ser Val Pro Ile Gly Gln Ser Val Asn 85 90 95Leu Val Leu Cys Arg Gly Tyr Pro 10021693PRTHuman papillomavirus 216His Tyr Lys Glu Leu Asp Val His Leu Arg Arg Met Glu Ser Gly Phe1 5 10 15Gly Phe Arg Ile Leu Gly Gly Asp Glu Pro Gly Gln Pro Ile Leu Ile 20 25 30Gly Ala Val Ile Ala Met Gly Ser Ala Asp Arg Asp Gly Arg Leu His 35 40 45Pro Gly Asp Glu Leu Val Tyr Val Asp Gly Ile Pro Val Ala Gly Lys 50 55 60Thr His Arg Tyr Val Ile Asp Leu Met His His Ala Ala Arg Asn Gly65 70 75 80Gln Val Asn Leu Thr Val Arg Arg Lys Val Leu Cys Gly 85 90217106PRTHuman papillomavirus 217Glu Gly Arg Gly Ile Ser Ser His Ser Leu Gln Thr Ser Asp Ala Val1 5 10 15Ile His Arg Lys Glu Asn Glu Gly Phe Gly Phe Val Ile Ile Ser Ser 20 25 30Leu Asn Arg Pro Glu Ser Gly Ser Thr Ile Thr Val Pro His Lys Ile 35 40 45Gly Arg Ile Ile Asp Gly Ser Pro Ala Asp Arg Cys Ala Lys Leu Lys 50 55 60Val Gly Asp Arg Ile Leu Ala Val Asn Gly Gln Ser Ile Ile Asn Met65 70 75 80Pro His Ala Asp Ile Val Lys Leu Ile Lys Asp Ala Gly Leu Ser Val 85 90 95Thr Leu Arg Ile Ile Pro Gln Glu Glu Leu 100 10521891PRTHuman papillomavirus 218Leu Ser Gly Ala Thr Gln Ala Glu Leu Met Thr Leu Thr Ile Val Lys1 5 10 15Gly Ala Gln Gly Phe Gly Phe Thr Ile Ala Asp Ser Pro Thr Gly Gln 20 25 30Arg Val Lys Gln Ile Leu Asp Ile Gln Gly Cys Pro Gly Leu Cys Glu 35 40 45Gly Asp Leu Ile Val Glu Ile Asn Gln Gln Asn Val Gln Asn Leu Ser 50 55 60His Thr Glu Val Val Asp Ile Leu Lys Asp Cys Pro Ile Gly Ser Glu65 70 75 80Thr Ser Leu Ile Ile His Arg Gly Gly Phe Phe 85 9021998PRTHuman papillomavirus 219Leu Ser Asp Tyr Arg Gln Pro Gln Asp Phe Asp Tyr Phe Thr Val Asp1 5 10 15Met Glu Lys Gly Ala Lys Gly Phe Gly Phe Ser Ile Arg Gly Gly Arg 20 25 30Glu Tyr Lys Met Asp Leu Tyr Val Leu Arg Leu Ala Glu Asp Gly Pro 35 40 45Ala Ile Arg Asn Gly Arg Met Arg Val Gly Asp Gln Ile Ile Glu Ile 50 55 60Asn Gly Glu Ser Thr Arg Asp Met Thr His Ala Arg Ala Ile Glu Leu65 70 75 80Ile Lys Ser Gly Gly Arg Arg Val Arg Leu Leu Leu Lys Arg Gly Thr 85 90 95Gly Gln22090PRTHuman papillomavirus 220His Glu Ser Val Ile Gly Arg Asn Pro Glu Gly Gln Leu Gly Phe Glu1 5 10 15Leu Lys Gly Gly Ala Glu Asn Gly Gln Phe Pro Tyr Leu Gly Glu Val 20 25 30Lys Pro Gly Lys Val Ala Tyr Glu Ser Gly Ser Lys Leu Val Ser Glu 35 40 45Glu Leu Leu Leu Glu Val Asn Glu Thr Pro Val Ala Gly Leu Thr Ile 50 55 60Arg Asp Val Leu Ala Val Ile Lys His Cys Lys Asp Pro Leu Arg Leu65 70 75 80Lys Cys Val Lys Gln Gly Gly Ile His Arg 85 90221100PRTHuman papillomavirus 221Ala Ser Ser Gly Ser Ser Gln Pro Glu Leu Val Thr Ile Pro Leu Ile1 5 10 15Lys Gly Pro Lys Gly Phe Gly Phe Ala Ile Ala Asp Ser Pro Thr Gly 20 25 30Gln Lys Val Lys Met Ile Leu Asp Ser Gln Trp Cys Gln Gly Leu Gln 35 40 45Lys Gly Asp Ile Ile Lys Glu Ile Tyr His Gln Asn Val Gln Asn Leu 50 55 60Thr His Leu Gln Val Val Glu Val Leu Lys Gln Phe Pro Val Gly Ala65 70 75 80Asp Val Pro Leu Leu Ile Leu Arg Gly Gly Pro Pro Ser Pro Thr Lys 85 90 95Thr Ala Lys Met 10022298PRTHuman papillomavirus 222Gln Asn Leu Gly Cys Tyr Pro Val Glu Leu Glu Arg Gly Pro Arg Gly1 5 10 15Phe Gly Phe Ser Leu Arg Gly Gly Lys Glu Tyr Asn Met Gly Leu Phe 20 25 30Ile Leu Arg Leu Ala Glu Asp Gly Pro Ala Ile Lys Asp Gly Arg Ile 35 40 45His Val Gly Asp Gln Ile Val Glu Ile Asn Gly Glu Pro Thr Gln Gly 50 55 60Ile Thr His Thr Arg Ala Ile Glu Leu Ile Gln Ala Gly Gly Asn Lys65

70 75 80Val Leu Leu Leu Leu Arg Pro Gly Thr Gly Leu Ile Pro Asp His Gly 85 90 95Leu Ala223108PRTHuman papillomavirus 223Leu Tyr Glu Asp Lys Pro Pro Asn Thr Lys Asp Leu Asp Val Phe Leu1 5 10 15Arg Lys Gln Glu Ser Gly Phe Gly Phe Arg Val Leu Gly Gly Asp Gly 20 25 30Pro Asp Gln Ser Ile Tyr Ile Gly Ala Ile Ile Pro Leu Gly Ala Ala 35 40 45Glu Lys Asp Gly Arg Leu Arg Ala Ala Asp Glu Leu Met Cys Ile Asp 50 55 60Gly Ile Pro Val Lys Gly Lys Ser His Lys Gln Val Leu Asp Leu Met65 70 75 80Thr Thr Ala Ala Arg Asn Gly His Val Leu Leu Thr Val Arg Arg Lys 85 90 95Ile Phe Tyr Gly Glu Lys Gln Pro Glu Asp Asp Ser 100 105224102PRTHuman papillomavirus 224Pro Ser Gln Leu Lys Gly Val Leu Val Arg Ala Ser Leu Lys Lys Ser1 5 10 15Thr Met Gly Phe Gly Phe Thr Ile Ile Gly Gly Asp Arg Pro Asp Glu 20 25 30Phe Leu Gln Val Lys Asn Val Leu Lys Asp Gly Pro Ala Ala Gln Asp 35 40 45Gly Lys Ile Ala Pro Gly Asp Val Ile Val Asp Ile Asn Gly Asn Cys 50 55 60Val Leu Gly His Thr His Ala Asp Val Val Gln Met Phe Gln Leu Val65 70 75 80Pro Val Asn Gln Tyr Val Asn Leu Thr Leu Cys Arg Gly Tyr Pro Leu 85 90 95Pro Asp Asp Ser Glu Asp 100225102PRTHuman papillomavirus 225Pro Ala Pro Gln Glu Pro Tyr Asp Val Val Leu Gln Arg Lys Glu Asn1 5 10 15Glu Gly Phe Gly Phe Val Ile Leu Thr Ser Lys Asn Lys Pro Pro Pro 20 25 30Gly Val Ile Pro His Lys Ile Gly Arg Val Ile Glu Gly Ser Pro Ala 35 40 45Asp Arg Cys Gly Lys Leu Lys Val Gly Asp His Ile Ser Ala Val Asn 50 55 60Gly Gln Ser Ile Val Glu Leu Ser His Asp Asn Ile Val Gln Leu Ile65 70 75 80Lys Asp Ala Gly Val Thr Val Thr Leu Thr Val Ile Ala Glu Glu Glu 85 90 95His His Gly Pro Pro Ser 10022694PRTHuman papillomavirus 226Gly Leu Arg Ser Pro Ile Thr Ile Gln Arg Ser Gly Lys Lys Tyr Gly1 5 10 15Phe Thr Leu Arg Ala Ile Arg Val Tyr Met Gly Asp Thr Asp Val Tyr 20 25 30Ser Val His His Ile Val Trp His Val Glu Glu Gly Gly Pro Ala Gln 35 40 45Glu Ala Gly Leu Cys Ala Gly Asp Leu Ile Thr His Val Asn Gly Glu 50 55 60Pro Val His Gly Met Val His Pro Glu Val Val Glu Leu Ile Leu Lys65 70 75 80Ser Gly Asn Lys Val Ala Val Thr Thr Thr Pro Phe Glu Asn 85 90227101PRTHuman papillomavirus 227Ile Ser Ala Leu Gly Ser Met Arg Pro Pro Ile Ile Ile His Arg Ala1 5 10 15Gly Lys Lys Tyr Gly Phe Thr Leu Arg Ala Ile Arg Val Tyr Met Gly 20 25 30Asp Ser Asp Val Tyr Thr Val His His Met Val Trp His Val Glu Asp 35 40 45Gly Gly Pro Ala Ser Glu Ala Gly Leu Arg Gln Gly Asp Leu Ile Thr 50 55 60His Val Asn Gly Glu Pro Val His Gly Leu Val His Thr Glu Val Val65 70 75 80Glu Leu Ile Leu Lys Ser Gly Asn Lys Val Ala Ile Ser Thr Thr Pro 85 90 95Leu Glu Asn Ser Ser 100228103PRTHuman papillomavirus 228Leu Cys Gly Ser Leu Arg Pro Pro Ile Val Ile His Ser Ser Gly Lys1 5 10 15Lys Tyr Gly Phe Ser Leu Arg Ala Ile Arg Val Tyr Met Gly Asp Ser 20 25 30Asp Val Tyr Thr Val His His Val Val Trp Ser Val Glu Asp Gly Ser 35 40 45Pro Ala Gln Glu Ala Gly Leu Arg Ala Gly Asp Leu Ile Thr His Ile 50 55 60Asn Gly Glu Ser Val Leu Gly Leu Val His Met Asp Val Val Glu Leu65 70 75 80Leu Leu Lys Ser Gly Asn Lys Ile Ser Leu Arg Thr Thr Ala Leu Glu 85 90 95Asn Thr Ser Ile Lys Val Gly 10022991PRTHuman papillomavirus 229Pro His Gln Pro Ile Val Ile His Ser Ser Gly Lys Asn Tyr Gly Phe1 5 10 15Thr Ile Arg Ala Ile Arg Val Tyr Val Gly Asp Ser Asp Ile Tyr Thr 20 25 30Val His His Ile Val Trp Asn Val Glu Glu Gly Ser Pro Ala Cys Gln 35 40 45Ala Gly Leu Lys Ala Gly Asp Leu Ile Thr His Ile Asn Gly Glu Pro 50 55 60Val His Gly Leu Val His Thr Glu Val Ile Glu Leu Leu Leu Lys Ser65 70 75 80Gly Asn Lys Val Ser Ile Thr Thr Thr Pro Phe 85 90230100PRTHuman papillomavirus 230Pro Ala Lys Met Glu Lys Glu Glu Thr Thr Arg Glu Leu Leu Leu Pro1 5 10 15Asn Trp Gln Gly Ser Gly Ser His Gly Leu Thr Ile Ala Gln Arg Asp 20 25 30Asp Gly Val Phe Val Gln Glu Val Thr Gln Asn Ser Pro Ala Ala Arg 35 40 45Thr Gly Val Val Lys Glu Gly Asp Gln Ile Val Gly Ala Thr Ile Tyr 50 55 60Phe Asp Asn Leu Gln Ser Gly Glu Val Thr Gln Leu Leu Asn Thr Met65 70 75 80Gly His His Thr Val Gly Leu Lys Leu His Arg Lys Gly Asp Arg Ser 85 90 95Pro Asn Ser Ser 10023198PRTHuman papillomavirus 231Ser Glu Asn Cys Lys Asp Val Phe Ile Glu Lys Gln Lys Gly Glu Ile1 5 10 15Leu Gly Val Val Ile Val Glu Ser Gly Trp Gly Ser Ile Leu Pro Thr 20 25 30Val Ile Ile Ala Asn Met Met His Gly Gly Pro Ala Glu Lys Ser Gly 35 40 45Lys Leu Asn Ile Gly Asp Gln Ile Met Ser Ile Asn Gly Thr Ser Leu 50 55 60Val Gly Leu Pro Leu Ser Thr Cys Gln Ser Ile Ile Lys Gly Leu Lys65 70 75 80Asn Gln Ser Arg Val Lys Leu Asn Ile Val Arg Cys Pro Pro Val Asn 85 90 95Ser Ser232178PRTHuman papillomavirus 232Ser Glu Asn Cys Lys Asp Val Phe Ile Glu Lys Gln Lys Gly Glu Ile1 5 10 15Leu Gly Val Val Ile Val Glu Ser Gly Trp Gly Ser Ile Leu Pro Thr 20 25 30Val Ile Ile Ala Asn Met Met His Gly Gly Pro Ala Glu Lys Ser Gly 35 40 45Lys Leu Asn Ile Gly Asp Gln Ile Met Ser Ile Asn Gly Thr Ser Leu 50 55 60Val Gly Leu Pro Leu Ser Thr Cys Gln Ser Ile Ile Lys Gly Leu Glu65 70 75 80Asn Gln Ser Arg Val Lys Leu Asn Ile Val Arg Cys Pro Pro Val Thr 85 90 95Thr Val Leu Ile Arg Arg Pro Asp Leu Arg Tyr Gln Leu Gly Phe Ser 100 105 110Val Gln Asn Gly Ile Ile Cys Ser Leu Met Arg Gly Gly Ile Ala Glu 115 120 125Arg Gly Gly Val Arg Val Gly His Arg Ile Ile Glu Ile Asn Gly Gln 130 135 140Ser Val Val Ala Thr Pro His Glu Lys Ile Val His Ile Leu Ser Asn145 150 155 160Ala Val Gly Glu Ile His Met Lys Thr Met Pro Ala Ala Met Tyr Arg 165 170 175Leu Leu23392PRTHuman papillomavirus 233Leu Arg Cys Pro Pro Val Thr Thr Val Leu Ile Arg Arg Pro Asp Leu1 5 10 15Arg Tyr Gln Leu Gly Phe Ser Val Gln Asn Gly Ile Ile Cys Ser Leu 20 25 30Met Arg Gly Gly Ile Ala Glu Arg Gly Gly Val Arg Val Gly His Arg 35 40 45Ile Ile Glu Ile Asn Gly Gln Ser Val Val Ala Thr Pro His Glu Lys 50 55 60Ile Val His Ile Leu Ser Asn Ala Val Gly Glu Ile His Met Lys Thr65 70 75 80Met Pro Ala Ala Met Tyr Arg Leu Leu Asn Ser Ser 85 90234106PRTHuman papillomavirus 234His Asn Gly Asp Leu Asp His Phe Ser Asn Ser Asp Asn Cys Arg Glu1 5 10 15Val His Leu Glu Lys Arg Arg Gly Glu Gly Leu Gly Val Ala Leu Val 20 25 30Glu Ser Gly Trp Gly Ser Leu Leu Pro Thr Ala Val Ile Ala Asn Leu 35 40 45Leu His Gly Gly Pro Ala Glu Arg Ser Gly Ala Leu Ser Ile Gly Asp 50 55 60Arg Leu Thr Ala Ile Asn Gly Thr Ser Leu Val Gly Leu Pro Leu Ala65 70 75 80Ala Cys Gln Ala Ala Val Arg Glu Thr Lys Ser Gln Thr Ser Val Thr 85 90 95Leu Ser Ile Val His Cys Pro Pro Val Thr 100 10523590PRTHuman papillomavirus 235Pro Val Thr Thr Ala Ile Ile His Arg Pro His Ala Arg Glu Gln Leu1 5 10 15Gly Phe Cys Val Glu Asp Gly Ile Ile Cys Ser Leu Leu Arg Gly Gly 20 25 30Ile Ala Glu Arg Gly Gly Ile Arg Val Gly His Arg Ile Ile Glu Ile 35 40 45Asn Gly Gln Ser Val Val Ala Thr Pro His Ala Arg Ile Ile Glu Leu 50 55 60Leu Thr Glu Ala Tyr Gly Glu Val His Ile Lys Thr Met Pro Ala Ala65 70 75 80Thr Tyr Arg Leu Leu Thr Gly Asn Ser Ser 85 90236103PRTHuman papillomavirus 236Leu Ser Asn Ser Asp Asn Cys Arg Glu Val His Leu Glu Lys Arg Arg1 5 10 15Gly Glu Gly Leu Gly Val Ala Leu Val Glu Ser Gly Trp Gly Ser Leu 20 25 30Leu Pro Thr Ala Val Ile Ala Asn Leu Leu His Gly Gly Pro Ala Glu 35 40 45Arg Ser Gly Ala Leu Ser Ile Gly Asp Arg Leu Thr Ala Ile Asn Gly 50 55 60Thr Ser Leu Val Gly Leu Pro Leu Ala Ala Cys Gln Ala Ala Val Arg65 70 75 80Glu Thr Lys Ser Gln Thr Ser Val Thr Leu Ser Ile Val His Cys Pro 85 90 95Pro Val Thr Thr Ala Ile Met 10023786PRTHuman papillomavirus 237Arg Lys Val Arg Leu Ile Gln Phe Glu Lys Val Thr Glu Glu Pro Met1 5 10 15Gly Ile Thr Leu Lys Leu Asn Glu Lys Gln Ser Cys Thr Val Ala Arg 20 25 30Ile Leu His Gly Gly Met Ile His Arg Gln Gly Ser Leu His Val Gly 35 40 45Asp Glu Ile Leu Glu Ile Asn Gly Thr Asn Val Thr Asn His Ser Val 50 55 60Asp Gln Leu Gln Lys Ala Met Lys Glu Thr Lys Gly Met Ile Ser Leu65 70 75 80Lys Val Ile Pro Asn Gln 8523889PRTHuman papillomavirus 238Pro Val Pro Pro Asp Ala Val Arg Met Val Gly Ile Arg Lys Thr Ala1 5 10 15Gly Glu His Leu Gly Val Thr Phe Arg Val Glu Gly Gly Glu Leu Val 20 25 30Ile Ala Arg Ile Leu His Gly Gly Met Val Ala Gln Gln Gly Leu Leu 35 40 45His Val Gly Asp Ile Ile Lys Glu Val Asn Gly Gln Pro Val Gly Ser 50 55 60Asp Pro Arg Ala Leu Gln Glu Leu Leu Arg Asn Ala Ser Gly Ser Val65 70 75 80Ile Leu Lys Ile Leu Pro Asn Tyr Gln 8523999PRTHuman papillomavirus 239Asn Ile Asp Glu Asp Phe Asp Glu Glu Ser Val Lys Ile Val Arg Leu1 5 10 15Val Lys Asn Lys Glu Pro Leu Gly Ala Thr Ile Arg Arg Asp Glu His 20 25 30Ser Gly Ala Val Val Val Ala Arg Ile Met Arg Gly Gly Ala Ala Asp 35 40 45Arg Ser Gly Leu Val His Val Gly Asp Glu Leu Arg Glu Val Asn Gly 50 55 60Ile Ala Val Leu His Lys Arg Pro Asp Glu Ile Ser Gln Ile Leu Ala65 70 75 80Gln Ser Gln Gly Ser Ile Thr Leu Lys Ile Ile Pro Ala Thr Gln Glu 85 90 95Glu Asp Arg240100PRTHuman papillomavirus 240Trp Glu Ala Gly Ile Gln His Ile Glu Leu Glu Lys Gly Ser Lys Gly1 5 10 15Leu Gly Phe Ser Ile Leu Asp Tyr Gln Asp Pro Ile Asp Pro Ala Ser 20 25 30Thr Val Ile Ile Ile Arg Ser Leu Val Pro Gly Gly Ile Ala Glu Lys 35 40 45Asp Gly Arg Leu Leu Pro Gly Asp Arg Leu Met Phe Val Asn Asp Val 50 55 60Asn Leu Glu Asn Ser Ser Leu Glu Glu Ala Val Glu Ala Leu Lys Gly65 70 75 80Ala Pro Ser Gly Thr Val Arg Ile Gly Val Ala Lys Pro Leu Pro Leu 85 90 95Ser Pro Glu Glu 10024196PRTHuman papillomavirus 241Leu Gln Gly Leu Arg Thr Val Glu Met Lys Lys Gly Pro Thr Asp Ser1 5 10 15Leu Gly Ile Ser Ile Ala Gly Gly Val Gly Ser Pro Leu Gly Asp Val 20 25 30Pro Ile Phe Ile Ala Met Met His Pro Thr Gly Val Ala Ala Gln Thr 35 40 45Gln Lys Leu Arg Val Gly Asp Arg Ile Val Thr Ile Cys Gly Thr Ser 50 55 60Thr Glu Gly Met Thr His Thr Gln Ala Val Asn Leu Leu Lys Asn Ala65 70 75 80Ser Gly Ser Ile Glu Met Gln Val Val Ala Gly Gly Asp Val Ser Val 85 90 9524297PRTHuman papillomavirus 242Pro Val His Trp Gln His Met Glu Thr Ile Glu Leu Val Asn Asp Gly1 5 10 15Ser Gly Leu Gly Phe Gly Ile Ile Gly Gly Lys Ala Thr Gly Val Ile 20 25 30Val Lys Thr Ile Leu Pro Gly Gly Val Ala Asp Gln His Gly Arg Leu 35 40 45Cys Ser Gly Asp His Ile Leu Lys Ile Gly Asp Thr Asp Leu Ala Gly 50 55 60Met Ser Ser Glu Gln Val Ala Gln Val Leu Arg Gln Cys Gly Asn Arg65 70 75 80Val Lys Leu Met Ile Ala Arg Gly Ala Ile Glu Glu Arg Thr Ala Pro 85 90 95Thr24398PRTHuman papillomavirus 243Gln Glu Ser Glu Thr Phe Asp Val Glu Leu Thr Lys Asn Val Gln Gly1 5 10 15Leu Gly Ile Thr Ile Ala Gly Tyr Ile Gly Asp Lys Lys Leu Glu Pro 20 25 30Ser Gly Ile Phe Val Lys Ser Ile Thr Lys Ser Ser Ala Val Glu His 35 40 45Asp Gly Arg Ile Gln Ile Gly Asp Gln Ile Ile Ala Val Asp Gly Thr 50 55 60Asn Leu Gln Gly Phe Thr Asn Gln Gln Ala Val Glu Val Leu Arg His65 70 75 80Thr Gly Gln Thr Val Leu Leu Thr Leu Met Arg Arg Gly Met Lys Gln 85 90 95Glu Ala24498PRTHuman papillomavirus 244Lys Glu Glu Glu Val Cys Asp Thr Leu Thr Ile Glu Leu Gln Lys Lys1 5 10 15Pro Gly Lys Gly Leu Gly Leu Ser Ile Val Gly Lys Arg Asn Asp Thr 20 25 30Gly Val Phe Val Ser Asp Ile Val Lys Gly Gly Ile Ala Asp Ala Asp 35 40 45Gly Arg Leu Met Gln Gly Asp Gln Ile Leu Met Val Asn Gly Glu Asp 50 55 60Val Arg Asn Ala Thr Gln Glu Ala Val Ala Ala Leu Leu Lys Cys Ser65 70 75 80Leu Gly Thr Val Thr Leu Glu Val Gly Arg Ile Lys Ala Gly Pro Phe 85 90 95His Ser24595PRTHuman papillomavirus 245Leu Thr Gly Glu Leu His Met Ile Glu Leu Glu Lys Gly His Ser Gly1 5 10 15Leu Gly Leu Ser Leu Ala Gly Asn Lys Asp Arg Ser Arg Met Ser Val 20 25 30Phe Ile Val Gly Ile Asp Pro Asn Gly Ala Ala Gly Lys Asp Gly Arg 35 40 45Leu Gln Ile Ala Asp Glu Leu Leu Glu Ile Asn Gly Gln Ile Leu Tyr 50 55 60Gly Arg Ser His Gln Asn Ala Ser Ser Ile Ile Lys Cys Ala Pro Ser65 70 75 80Lys Val Lys Ile Ile Phe Ile Arg Asn Lys Asp Ala Val Asn Gln 85 90 9524691PRTHuman papillomavirus 246Leu Gly Pro Pro Gln Cys Lys Ser Ile Thr Leu Glu Arg Gly Pro Asp1 5 10 15Gly Leu Gly Phe Ser Ile Val Gly Gly Tyr Gly Ser Pro His Gly Asp 20 25 30Leu Pro Ile Tyr Val Lys Thr Val Phe Ala Lys Gly Ala

Ala Ser Glu 35 40 45Asp Gly Arg Leu Lys Arg Gly Asp Gln Ile Ile Ala Val Asn Gly Gln 50 55 60Ser Leu Glu Gly Val Thr His Glu Glu Ala Val Ala Ile Leu Lys Arg65 70 75 80Thr Lys Gly Thr Val Thr Leu Met Val Leu Ser 85 9024799PRTHuman papillomavirus 247Arg Asn Val Ser Lys Glu Ser Phe Glu Arg Thr Ile Asn Ile Ala Lys1 5 10 15Gly Asn Ser Ser Leu Gly Met Thr Val Ser Ala Asn Lys Asp Gly Leu 20 25 30Gly Met Ile Val Arg Ser Ile Ile His Gly Gly Ala Ile Ser Arg Asp 35 40 45Gly Arg Ile Ala Ile Gly Asp Cys Ile Leu Ser Ile Asn Glu Glu Ser 50 55 60Thr Ile Ser Val Thr Asn Ala Gln Ala Arg Ala Met Leu Arg Arg His65 70 75 80Ser Leu Ile Gly Pro Asp Ile Lys Ile Thr Tyr Val Pro Ala Glu His 85 90 95Leu Glu Glu24895PRTHuman papillomavirus 248Leu Pro Gly Cys Glu Thr Thr Ile Glu Ile Ser Lys Gly Arg Thr Gly1 5 10 15Leu Gly Leu Ser Ile Val Gly Gly Ser Asp Thr Leu Leu Gly Ala Ile 20 25 30Ile Ile His Glu Val Tyr Glu Glu Gly Ala Ala Cys Lys Asp Gly Arg 35 40 45Leu Trp Ala Gly Asp Gln Ile Leu Glu Val Asn Gly Ile Asp Leu Arg 50 55 60Lys Ala Thr His Asp Glu Ala Ile Asn Val Leu Arg Gln Thr Pro Gln65 70 75 80Arg Val Arg Leu Thr Leu Tyr Arg Asp Glu Ala Pro Tyr Lys Glu 85 90 95249112PRTHuman papillomavirus 249Leu Asn Trp Asn Gln Pro Arg Arg Val Glu Leu Trp Arg Glu Pro Ser1 5 10 15Lys Ser Leu Gly Ile Ser Ile Val Gly Gly Arg Gly Met Gly Ser Arg 20 25 30Leu Ser Asn Gly Glu Val Met Arg Gly Ile Phe Ile Lys His Val Leu 35 40 45Glu Asp Ser Pro Ala Gly Lys Asn Gly Thr Leu Lys Pro Gly Asp Arg 50 55 60Ile Val Glu Val Asp Gly Met Asp Leu Arg Asp Ala Ser His Glu Gln65 70 75 80Ala Val Glu Ala Ile Arg Lys Ala Gly Asn Pro Val Val Phe Met Val 85 90 95Gln Ser Ile Ile Asn Arg Pro Arg Lys Ser Pro Leu Pro Ser Leu Leu 100 105 11025094PRTHuman papillomavirus 250Leu Ser Ser Phe Lys Asn Val Gln His Leu Glu Leu Pro Lys Asp Gln1 5 10 15Gly Gly Leu Gly Ile Ala Ile Ser Glu Glu Asp Thr Leu Ser Gly Val 20 25 30Ile Ile Lys Ser Leu Thr Glu His Gly Val Ala Ala Thr Asp Gly Arg 35 40 45Leu Lys Val Gly Asp Gln Ile Leu Ala Val Asp Asp Glu Ile Val Val 50 55 60Gly Tyr Pro Ile Glu Lys Phe Ile Ser Leu Leu Lys Thr Ala Lys Met65 70 75 80Thr Val Lys Leu Thr Ile His Ala Glu Asn Pro Asp Ser Gln 85 9025199PRTHuman papillomavirus 251Gln Gly Arg His Val Glu Val Phe Glu Leu Leu Lys Pro Pro Ser Gly1 5 10 15Gly Leu Gly Phe Ser Val Val Gly Leu Arg Ser Glu Asn Arg Gly Glu 20 25 30Leu Gly Ile Phe Val Gln Glu Ile Gln Glu Gly Ser Val Ala His Arg 35 40 45Asp Gly Arg Leu Lys Glu Thr Asp Gln Ile Leu Ala Ile Asn Gly Gln 50 55 60Ala Leu Asp Gln Thr Ile Thr His Gln Gln Ala Ile Ser Ile Leu Gln65 70 75 80Lys Ala Lys Asp Thr Val Gln Leu Val Ile Ala Arg Gly Ser Leu Pro 85 90 95Gln Leu Val25292PRTHuman papillomavirus 252Leu Asn Tyr Glu Ile Val Val Ala His Val Ser Lys Phe Ser Glu Asn1 5 10 15Ser Gly Leu Gly Ile Ser Leu Glu Ala Thr Val Gly His His Phe Ile 20 25 30Arg Ser Val Leu Pro Glu Gly Pro Val Gly His Ser Gly Lys Leu Phe 35 40 45Ser Gly Asp Glu Leu Leu Glu Val Asn Gly Ile Thr Leu Leu Gly Glu 50 55 60Asn His Gln Asp Val Val Asn Ile Leu Lys Glu Leu Pro Ile Glu Val65 70 75 80Thr Met Val Cys Cys Arg Arg Thr Val Pro Pro Thr 85 9025390PRTHuman papillomavirus 253Ile Thr Leu Leu Lys Gly Pro Lys Gly Leu Gly Phe Ser Ile Ala Gly1 5 10 15Gly Ile Gly Asn Gln His Ile Pro Gly Asp Asn Ser Ile Tyr Ile Thr 20 25 30Lys Ile Ile Glu Gly Gly Ala Ala Gln Lys Asp Gly Arg Leu Gln Ile 35 40 45Gly Asp Arg Leu Leu Ala Val Asn Asn Thr Asn Leu Gln Asp Val Arg 50 55 60His Glu Glu Ala Val Ala Ser Leu Lys Asn Thr Ser Asp Met Val Tyr65 70 75 80Leu Lys Val Ala Lys Pro Gly Ser Leu Glu 85 9025493PRTHuman papillomavirus 254Ile Gln Tyr Glu Glu Ile Val Leu Glu Arg Gly Asn Ser Gly Leu Gly1 5 10 15Phe Ser Ile Ala Gly Gly Ile Asp Asn Pro His Val Pro Asp Asp Pro 20 25 30Gly Ile Phe Ile Thr Lys Ile Ile Pro Gly Gly Ala Ala Ala Met Asp 35 40 45Gly Arg Leu Gly Val Asn Asp Cys Val Leu Arg Val Asn Glu Val Glu 50 55 60Val Ser Glu Val Val His Ser Arg Ala Val Glu Ala Leu Lys Glu Ala65 70 75 80Gly Pro Val Val Arg Leu Val Val Arg Arg Arg Gln Asn 85 90255119PRTHuman papillomavirus 255Ile Leu Leu His Lys Gly Ser Thr Gly Leu Gly Phe Asn Ile Val Gly1 5 10 15Gly Glu Asp Gly Glu Gly Ile Phe Val Ser Phe Ile Leu Ala Gly Gly 20 25 30Pro Ala Asp Leu Ser Gly Glu Leu Arg Arg Gly Asp Arg Ile Leu Ser 35 40 45Val Asn Gly Val Asn Leu Arg Asn Ala Thr His Glu Gln Ala Ala Ala 50 55 60Ala Leu Lys Arg Ala Gly Gln Ser Val Thr Ile Val Ala Gln Tyr Arg65 70 75 80Pro Glu Glu Tyr Ser Arg Phe Glu Ser Lys Ile His Asp Leu Arg Glu 85 90 95Gln Met Met Asn Ser Ser Met Ser Ser Gly Ser Gly Ser Leu Arg Thr 100 105 110Ser Glu Lys Arg Ser Leu Glu 115256187PRTHuman papillomavirus 256Tyr Glu Glu Ile Val Leu Glu Arg Gly Asn Ser Gly Leu Gly Phe Ser1 5 10 15Ile Ala Gly Gly Ile Asp Asn Pro His Val Pro Asp Asp Pro Gly Ile 20 25 30Phe Ile Thr Lys Ile Ile Pro Gly Gly Ala Ala Ala Met Asp Gly Arg 35 40 45Leu Gly Val Asn Asp Cys Val Leu Arg Val Asn Glu Val Glu Val Ser 50 55 60Glu Val Val His Ser Arg Ala Val Glu Ala Leu Lys Glu Ala Gly Pro65 70 75 80Val Val Arg Leu Val Val Arg Arg Arg Gln Pro Pro Pro Glu Thr Ile 85 90 95Met Glu Val Asn Leu Leu Lys Gly Pro Lys Gly Leu Gly Phe Ser Ile 100 105 110Ala Gly Gly Ile Gly Asn Gln His Ile Pro Gly Asp Asn Ser Ile Tyr 115 120 125Ile Thr Lys Ile Ile Glu Gly Gly Ala Ala Gln Lys Asp Gly Arg Leu 130 135 140Gln Ile Gly Asp Arg Leu Leu Ala Val Asn Asn Thr Asn Leu Gln Asp145 150 155 160Val Arg His Glu Glu Ala Val Ala Ser Leu Lys Asn Thr Ser Asp Met 165 170 175Val Tyr Leu Lys Val Ala Lys Pro Gly Ser Leu 180 185257106PRTHuman papillomavirus 257Arg Val Glu Arg Leu Glu Leu Phe Pro Val Glu Leu Glu Lys Asp Ser1 5 10 15Glu Gly Leu Gly Ile Ser Ile Ile Gly Met Gly Ala Gly Ala Asp Met 20 25 30Gly Leu Glu Lys Leu Gly Ile Phe Val Lys Thr Val Thr Glu Gly Gly 35 40 45Ala Ala His Arg Asp Gly Arg Ile Gln Val Asn Asp Leu Leu Val Glu 50 55 60Val Asp Gly Thr Ser Leu Val Gly Val Thr Gln Ser Phe Ala Ala Ser65 70 75 80Val Leu Arg Asn Thr Lys Gly Arg Val Arg Cys Arg Phe Met Ile Gly 85 90 95Arg Glu Arg Pro Gly Glu Gln Ser Glu Val 100 10525890PRTHuman papillomavirus 258Gln Pro Asn Val Ile Ser Val Arg Leu Phe Lys Arg Lys Val Gly Gly1 5 10 15Leu Gly Phe Leu Val Lys Glu Arg Val Ser Lys Pro Pro Val Ile Ile 20 25 30Ser Asp Leu Ile Arg Gly Gly Ala Ala Glu Gln Ser Gly Leu Ile Gln 35 40 45Ala Gly Asp Ile Ile Leu Ala Val Asn Gly Arg Pro Leu Val Asp Leu 50 55 60Ser Tyr Asp Ser Ala Leu Glu Val Leu Arg Gly Ile Ala Ser Glu Thr65 70 75 80His Val Val Leu Ile Leu Arg Gly Pro Glu 85 90259103PRTHuman papillomavirus 259Pro Ser Asp Thr Ser Ser Glu Asp Gly Val Arg Arg Ile Val His Leu1 5 10 15Tyr Thr Thr Ser Asp Asp Phe Cys Leu Gly Phe Asn Ile Arg Gly Gly 20 25 30Lys Glu Phe Gly Leu Gly Ile Tyr Val Ser Lys Val Asp His Gly Gly 35 40 45Leu Ala Glu Glu Asn Gly Ile Lys Val Gly Asp Gln Val Leu Ala Ala 50 55 60Asn Gly Val Arg Phe Asp Asp Ile Ser His Ser Gln Ala Val Glu Val65 70 75 80Leu Lys Gly Gln Thr His Ile Met Leu Thr Ile Lys Glu Thr Gly Arg 85 90 95Tyr Pro Ala Tyr Lys Glu Met 100260104PRTHuman papillomavirus 260Glu Ala Asn Ser Asp Glu Ser Asp Ile Ile His Ser Val Arg Val Glu1 5 10 15Lys Ser Pro Ala Gly Arg Leu Gly Phe Ser Val Arg Gly Gly Ser Glu 20 25 30His Gly Leu Gly Ile Phe Val Ser Lys Val Glu Glu Gly Ser Ser Ala 35 40 45Glu Arg Ala Gly Leu Cys Val Gly Asp Lys Ile Thr Glu Val Asn Gly 50 55 60Leu Ser Leu Glu Ser Thr Thr Met Gly Ser Ala Val Lys Val Leu Thr65 70 75 80Ser Ser Ser Arg Leu His Met Met Val Arg Arg Met Gly Arg Val Pro 85 90 95Gly Ile Lys Phe Ser Lys Glu Lys 100261116PRTHuman papillomavirus 261Asp Lys Ile Lys Lys Phe Leu Thr Glu Ser His Asp Arg Gln Ala Lys1 5 10 15Gly Lys Ala Ile Thr Lys Lys Lys Tyr Ile Gly Ile Arg Met Met Ser 20 25 30Leu Thr Ser Ser Lys Ala Lys Glu Leu Lys Asp Arg His Arg Asp Phe 35 40 45Pro Asp Val Ile Ser Gly Ala Tyr Ile Ile Glu Val Ile Pro Asp Thr 50 55 60Pro Ala Glu Ala Gly Gly Leu Lys Glu Asn Asp Val Ile Ile Ser Ile65 70 75 80Asn Gly Gln Ser Val Val Ser Ala Asn Asp Val Ser Asp Val Ile Lys 85 90 95Arg Glu Ser Thr Leu Asn Met Val Val Arg Arg Gly Asn Glu Asp Ile 100 105 110Met Ile Thr Val 11526298PRTHuman papillomavirus 262Tyr Arg Pro Arg Asp Asp Ser Phe His Val Ile Leu Asn Lys Ser Ser1 5 10 15Pro Glu Glu Gln Leu Gly Ile Lys Leu Val Arg Lys Val Asp Glu Pro 20 25 30Gly Val Phe Ile Phe Asn Ala Leu Asp Gly Gly Val Ala Tyr Arg His 35 40 45Gly Gln Leu Glu Glu Asn Asp Arg Val Leu Ala Ile Asn Gly His Asp 50 55 60Leu Arg Tyr Gly Ser Pro Glu Ser Ala Ala His Leu Ile Gln Ala Ser65 70 75 80Glu Arg Arg Val His Leu Val Val Ser Arg Gln Val Arg Gln Arg Ser 85 90 95Pro Asp263100PRTHuman papillomavirus 263Pro Thr Ile Thr Cys His Glu Lys Val Val Asn Ile Gln Lys Asp Pro1 5 10 15Gly Glu Ser Leu Gly Met Thr Val Ala Gly Gly Ala Ser His Arg Glu 20 25 30Trp Asp Leu Pro Ile Tyr Val Ile Ser Val Glu Pro Gly Gly Val Ile 35 40 45Ser Arg Asp Gly Arg Ile Lys Thr Gly Asp Ile Leu Leu Asn Val Asp 50 55 60Gly Val Glu Leu Thr Glu Val Ser Arg Ser Glu Ala Val Ala Leu Leu65 70 75 80Lys Arg Thr Ser Ser Ser Ile Val Leu Lys Ala Leu Glu Val Lys Glu 85 90 95Tyr Glu Pro Gln 10026497PRTHuman papillomavirus 264Pro Asp Gly Glu Ile Thr Ser Ile Lys Ile Asn Arg Val Asp Pro Ser1 5 10 15Glu Ser Leu Ser Ile Arg Leu Val Gly Gly Ser Glu Thr Pro Leu Val 20 25 30His Ile Ile Ile Gln His Ile Tyr Arg Asp Gly Val Ile Ala Arg Asp 35 40 45Gly Arg Leu Leu Pro Arg Asp Ile Ile Leu Lys Val Asn Gly Met Asp 50 55 60Ile Ser Asn Val Pro His Asn Tyr Ala Val Arg Leu Leu Arg Gln Pro65 70 75 80Cys Gln Val Leu Trp Leu Thr Val Met Arg Glu Gln Lys Phe Arg Ser 85 90 95Arg26599PRTHuman papillomavirus 265Pro Arg Cys Leu Tyr Asn Cys Lys Asp Ile Val Leu Arg Arg Asn Thr1 5 10 15Ala Gly Ser Leu Gly Phe Cys Ile Val Gly Gly Tyr Glu Glu Tyr Asn 20 25 30Gly Asn Lys Pro Phe Phe Ile Lys Ser Ile Val Glu Gly Thr Pro Ala 35 40 45Tyr Asn Asp Gly Arg Ile Arg Cys Gly Asp Ile Leu Leu Ala Val Asn 50 55 60Gly Arg Ser Thr Ser Gly Met Ile His Ala Cys Leu Ala Arg Leu Leu65 70 75 80Lys Glu Leu Lys Gly Arg Ile Thr Leu Thr Ile Val Ser Trp Pro Gly 85 90 95Thr Phe Leu266101PRTHuman papillomavirus 266Leu Leu Thr Glu Glu Glu Ile Asn Leu Thr Arg Gly Pro Ser Gly Leu1 5 10 15Gly Phe Asn Ile Val Gly Gly Thr Asp Gln Gln Tyr Val Ser Asn Asp 20 25 30Ser Gly Ile Tyr Val Ser Arg Ile Lys Glu Asn Gly Ala Ala Ala Leu 35 40 45Asp Gly Arg Leu Gln Glu Gly Asp Lys Ile Leu Ser Val Asn Gly Gln 50 55 60Asp Leu Lys Asn Leu Leu His Gln Asp Ala Val Asp Leu Phe Arg Asn65 70 75 80Ala Gly Tyr Ala Val Ser Leu Arg Val Gln His Arg Leu Gln Val Gln 85 90 95Asn Gly Ile His Ser 10026794PRTHuman papillomavirus 267Pro Val Asp Ala Ile Arg Ile Leu Gly Ile His Lys Arg Ala Gly Glu1 5 10 15Pro Leu Gly Val Thr Phe Arg Val Glu Asn Asn Asp Leu Val Ile Ala 20 25 30Arg Ile Leu His Gly Gly Met Ile Asp Arg Gln Gly Leu Leu His Val 35 40 45Gly Asp Ile Ile Lys Glu Val Asn Gly His Glu Val Gly Asn Asn Pro 50 55 60Lys Glu Leu Gln Glu Leu Leu Lys Asn Ile Ser Gly Ser Val Thr Leu65 70 75 80Lys Ile Leu Pro Ser Tyr Arg Asp Thr Ile Thr Pro Gln Gln 85 9026894PRTHuman papillomavirus 268Gly Lys Arg Leu Asn Ile Gln Leu Lys Lys Gly Thr Glu Gly Leu Gly1 5 10 15Phe Ser Ile Thr Ser Arg Asp Val Thr Ile Gly Gly Ser Ala Pro Ile 20 25 30Tyr Val Lys Asn Ile Leu Pro Arg Gly Ala Ala Ile Gln Asp Gly Arg 35 40 45Leu Lys Ala Gly Asp Arg Leu Ile Glu Val Asn Gly Val Asp Leu Val 50 55 60Gly Lys Ser Gln Glu Glu Val Val Ser Leu Leu Arg Ser Thr Lys Met65 70 75 80Glu Gly Thr Val Ser Leu Leu Val Phe Arg Gln Glu Asp Ala 85 90269106PRTHuman papillomavirus 269Ile Pro Asn Phe Ser Leu Asp Asp Met Val Lys Leu Val Glu Val Pro1 5 10 15Asn Asp Gly Gly Pro Leu Gly Ile His Val Val Pro Phe Ser Ala Arg 20 25 30Gly Gly Arg Thr Leu Gly Leu Leu Val Lys Arg Leu Glu Lys Gly Gly 35 40 45Lys Ala Glu His Glu Asn Leu Phe Arg Glu Asn Asp Cys Ile Val Arg 50 55 60Ile Asn Asp Gly Asp Leu Arg Asn Arg

Arg Phe Glu Gln Ala Gln His65 70 75 80Met Phe Arg Gln Ala Met Arg Thr Pro Ile Ile Trp Phe His Val Val 85 90 95Pro Ala Ala Asn Lys Glu Gln Tyr Glu Gln 100 105270113PRTHuman papillomavirus 270Pro Arg Glu Phe Leu Thr Phe Glu Val Pro Leu Asn Asp Ser Gly Ser1 5 10 15Ala Gly Leu Gly Val Ser Val Lys Gly Asn Arg Ser Lys Glu Asn His 20 25 30Ala Asp Leu Gly Ile Phe Val Lys Ser Ile Ile Asn Gly Gly Ala Ala 35 40 45Ser Lys Asp Gly Arg Leu Arg Val Asn Asp Gln Leu Ile Ala Val Asn 50 55 60Gly Glu Ser Leu Leu Gly Lys Thr Asn Gln Asp Ala Met Glu Thr Leu65 70 75 80Arg Arg Ser Met Ser Thr Glu Gly Asn Lys Arg Gly Met Ile Gln Leu 85 90 95Ile Val Ala Ser Arg Ile Ser Lys Cys Asn Glu Leu Lys Ser Asn Ser 100 105 110Ser27199PRTHuman papillomavirus 271Ile Ser Asn Lys Asn Ala Lys Lys Ile Lys Ile Asp Leu Lys Lys Gly1 5 10 15Pro Glu Gly Leu Gly Phe Thr Val Val Thr Arg Asp Ser Ser Ile His 20 25 30Gly Pro Gly Pro Ile Phe Val Lys Asn Ile Leu Pro Lys Gly Ala Ala 35 40 45Ile Lys Asp Gly Arg Leu Gln Ser Gly Asp Arg Ile Leu Glu Val Asn 50 55 60Gly Arg Asp Val Thr Gly Arg Thr Gln Glu Glu Leu Val Ala Met Leu65 70 75 80Arg Ser Thr Lys Gln Gly Glu Thr Ala Ser Leu Val Ile Ala Arg Gln 85 90 95Glu Gly His272106PRTHuman papillomavirus 272Ile Thr Ser Glu Gln Leu Thr Phe Glu Ile Pro Leu Asn Asp Ser Gly1 5 10 15Ser Ala Gly Leu Gly Val Ser Leu Lys Gly Asn Lys Ser Arg Glu Thr 20 25 30Gly Thr Asp Leu Gly Ile Phe Ile Lys Ser Ile Ile His Gly Gly Ala 35 40 45Ala Phe Lys Asp Gly Arg Leu Arg Met Asn Asp Gln Leu Ile Ala Val 50 55 60Asn Gly Glu Ser Leu Leu Gly Lys Ser Asn His Glu Ala Met Glu Thr65 70 75 80Leu Arg Arg Ser Met Ser Met Glu Gly Asn Ile Arg Gly Met Ile Gln 85 90 95Leu Val Ile Leu Arg Arg Pro Glu Arg Pro 100 105273104PRTHuman papillomavirus 273Ile Pro Arg Thr Lys Asp Thr Leu Ser Asp Met Thr Arg Thr Val Glu1 5 10 15Ile Ser Gly Glu Gly Gly Pro Leu Gly Ile His Val Val Pro Phe Phe 20 25 30Ser Ser Leu Ser Gly Arg Ile Leu Gly Leu Phe Ile Arg Gly Ile Glu 35 40 45Asp Asn Ser Arg Ser Lys Arg Glu Gly Leu Phe His Glu Asn Glu Cys 50 55 60Ile Val Lys Ile Asn Asn Val Asp Leu Val Asp Lys Thr Phe Ala Gln65 70 75 80Ala Gln Asp Val Phe Arg Gln Ala Met Lys Ser Pro Ser Val Leu Leu 85 90 95His Val Leu Pro Pro Gln Asn Arg 100274104PRTHuman papillomavirus 274Pro Glu Thr His Arg Arg Val Arg Leu His Lys His Gly Ser Asp Arg1 5 10 15Pro Leu Gly Phe Tyr Ile Arg Asp Gly Met Ser Val Arg Val Ala Pro 20 25 30Gln Gly Leu Glu Arg Val Pro Gly Ile Phe Ile Ser Arg Leu Val Arg 35 40 45Gly Gly Leu Ala Glu Ser Thr Gly Leu Leu Ala Val Ser Asp Glu Ile 50 55 60Leu Glu Val Asn Gly Ile Glu Val Ala Gly Lys Thr Leu Asp Gln Val65 70 75 80Thr Asp Met Met Val Ala Asn Ser His Asn Leu Ile Val Thr Val Lys 85 90 95Pro Ala Asn Gln Arg Asn Asn Val 100275120PRTHuman papillomavirus 275Ile Pro Val Ser Ser Ile Ile Asp Val Asp Ile Leu Pro Glu Thr His1 5 10 15Arg Arg Val Arg Leu Tyr Lys Tyr Gly Thr Glu Lys Pro Leu Gly Phe 20 25 30Tyr Ile Arg Asp Gly Ser Ser Val Arg Val Thr Pro His Gly Leu Glu 35 40 45Lys Val Pro Gly Ile Phe Ile Ser Arg Leu Val Pro Gly Gly Leu Ala 50 55 60Gln Ser Thr Gly Leu Leu Ala Val Asn Asp Glu Val Leu Glu Val Asn65 70 75 80Gly Ile Glu Val Ser Gly Lys Ser Leu Asp Gln Val Thr Asp Met Met 85 90 95Ile Ala Asn Ser Arg Asn Leu Ile Ile Thr Val Arg Pro Ala Asn Gln 100 105 110Arg Asn Asn Arg Ile His Arg Asp 115 120276111PRTHuman papillomavirus 276Ile Asp Val Asp Leu Val Pro Glu Thr His Arg Arg Val Arg Leu His1 5 10 15Arg His Gly Cys Glu Lys Pro Leu Gly Phe Tyr Ile Arg Asp Gly Ala 20 25 30Ser Val Arg Val Thr Pro His Gly Leu Glu Lys Val Pro Gly Ile Phe 35 40 45Ile Ser Arg Met Val Pro Gly Gly Leu Ala Glu Ser Thr Gly Leu Leu 50 55 60Ala Val Asn Asp Glu Val Leu Glu Val Asn Gly Ile Glu Val Ala Gly65 70 75 80Lys Thr Leu Asp Gln Val Thr Asp Met Met Ile Ala Asn Ser His Asn 85 90 95Leu Ile Val Thr Val Lys Pro Ala Asn Gln Arg Asn Asn Val Val 100 105 110277103PRTHuman papillomavirus 277Pro Glu Gln Ile Met Gly Lys Asp Val Arg Leu Leu Arg Ile Lys Lys1 5 10 15Glu Gly Ser Leu Asp Leu Ala Leu Glu Gly Gly Val Asp Ser Pro Ile 20 25 30Gly Lys Val Val Val Ser Ala Val Tyr Glu Arg Gly Ala Ala Glu Arg 35 40 45His Gly Gly Ile Val Lys Gly Asp Glu Ile Met Ala Ile Asn Gly Lys 50 55 60Ile Val Thr Asp Tyr Thr Leu Ala Glu Ala Asp Ala Ala Leu Gln Lys65 70 75 80Ala Trp Asn Gln Gly Gly Asp Trp Ile Asp Leu Val Val Ala Val Cys 85 90 95Pro Pro Lys Glu Tyr Asp Asp 100278102PRTHuman papillomavirus 278Ile Pro Gly Asn Arg Glu Asn Lys Glu Lys Lys Val Phe Ile Ser Leu1 5 10 15Val Gly Ser Arg Gly Leu Gly Cys Ser Ile Ser Ser Gly Pro Ile Gln 20 25 30Lys Pro Gly Ile Phe Ile Ser His Val Lys Pro Gly Ser Leu Ser Ala 35 40 45Glu Val Gly Leu Glu Ile Gly Asp Gln Ile Val Glu Val Asn Gly Val 50 55 60Asp Phe Ser Asn Leu Asp His Lys Glu Ala Val Asn Val Leu Lys Ser65 70 75 80Ser Arg Ser Leu Thr Ile Ser Ile Val Ala Ala Ala Gly Arg Glu Leu 85 90 95Phe Met Thr Asp Glu Phe 100279100PRTHuman papillomavirus 279Arg Ser Arg Lys Leu Lys Glu Val Arg Leu Asp Arg Leu His Pro Glu1 5 10 15Gly Leu Gly Leu Ser Val Arg Gly Gly Leu Glu Phe Gly Cys Gly Leu 20 25 30Phe Ile Ser His Leu Ile Lys Gly Gly Gln Ala Asp Ser Val Gly Leu 35 40 45Gln Val Gly Asp Glu Ile Val Arg Ile Asn Gly Tyr Ser Ile Ser Ser 50 55 60Cys Thr His Glu Glu Val Ile Asn Leu Ile Arg Thr Lys Lys Thr Val65 70 75 80Ser Ile Lys Val Arg His Ile Gly Leu Ile Pro Val Lys Ser Ser Pro 85 90 95Asp Glu Phe His 10028092PRTHuman papillomavirus 280Arg Leu Cys Tyr Leu Val Lys Glu Gly Gly Ser Tyr Gly Phe Ser Leu1 5 10 15Lys Thr Val Gln Gly Lys Lys Gly Val Tyr Met Thr Asp Ile Thr Pro 20 25 30Gln Gly Val Ala Met Arg Ala Gly Val Leu Ala Asp Asp His Leu Ile 35 40 45Glu Val Asn Gly Glu Asn Val Glu Asp Ala Ser His Glu Glu Val Val 50 55 60Glu Lys Val Lys Lys Ser Gly Ser Arg Val Met Phe Leu Leu Val Asp65 70 75 80Lys Glu Thr Asp Lys Arg Glu Phe Ile Val Thr Asp 85 90281112PRTHuman papillomavirus 281Gln Phe Lys Arg Glu Thr Ala Ser Leu Lys Leu Leu Pro His Gln Pro1 5 10 15Arg Ile Val Glu Met Lys Lys Gly Ser Asn Gly Tyr Gly Phe Tyr Leu 20 25 30Arg Ala Gly Ser Glu Gln Lys Gly Gln Ile Ile Lys Asp Ile Asp Ser 35 40 45Gly Ser Pro Ala Glu Glu Ala Gly Leu Lys Asn Asn Asp Leu Val Val 50 55 60Ala Val Asn Gly Glu Ser Val Glu Thr Leu Asp His Asp Ser Val Val65 70 75 80Glu Met Ile Arg Lys Gly Gly Asp Gln Thr Ser Leu Leu Val Val Asp 85 90 95Lys Glu Thr Asp Asn Met Tyr Arg Leu Ala Glu Phe Ile Val Thr Asp 100 105 110282324PRTHuman papillomavirus 282Arg Leu Cys Tyr Leu Val Lys Glu Gly Gly Ser Tyr Gly Phe Ser Leu1 5 10 15Lys Thr Val Gln Gly Lys Lys Gly Val Tyr Met Thr Asp Ile Thr Pro 20 25 30Gln Gly Val Ala Met Arg Ala Gly Val Leu Ala Asp Asp His Leu Ile 35 40 45Glu Val Asn Gly Glu Asn Val Glu Asp Ala Ser His Glu Lys Val Val 50 55 60Glu Lys Val Lys Lys Ser Gly Ser Arg Val Met Phe Leu Leu Val Asp65 70 75 80Lys Glu Thr Asp Lys Arg His Val Glu Gln Lys Ile Gln Phe Lys Arg 85 90 95Glu Thr Ala Ser Leu Lys Leu Leu Pro His Gln Pro Arg Ile Val Glu 100 105 110Met Lys Lys Gly Ser Asn Gly Tyr Gly Phe Tyr Leu Arg Ala Gly Ser 115 120 125Glu Gln Lys Gly Gln Ile Ile Lys Asp Ile Asp Ser Gly Ser Pro Ala 130 135 140Glu Glu Ala Gly Leu Lys Asn Asn Asp Leu Val Val Ala Val Asn Gly145 150 155 160Glu Ser Val Glu Thr Leu Asp His Asp Ser Val Val Glu Met Ile Arg 165 170 175Lys Gly Gly Asp Gln Thr Ser Leu Leu Val Val Asp Lys Glu Thr Asp 180 185 190Asn Met Tyr Arg Leu Ala His Phe Ser Pro Phe Leu Tyr Tyr Gln Ser 195 200 205Gln Glu Leu Pro Asn Gly Ser Val Lys Glu Ala Pro Ala Pro Thr Pro 210 215 220Thr Ser Leu Glu Val Ser Ser Pro Pro Asp Thr Thr Glu Glu Val Asp225 230 235 240His Lys Pro Lys Leu Cys Arg Leu Ala Lys Gly Glu Asn Gly Tyr Gly 245 250 255Phe His Leu Asn Ala Ile Arg Gly Leu Pro Gly Ser Phe Ile Lys Glu 260 265 270Val Gln Lys Gly Gly Pro Ala Asp Leu Ala Gly Leu Glu Asp Glu Asp 275 280 285Val Ile Ile Glu Val Asn Gly Val Asn Val Leu Asp Glu Pro Tyr Glu 290 295 300Lys Val Val Asp Arg Ile Gln Ser Ser Gly Lys Asn Val Thr Leu Leu305 310 315 320Val Cys Gly Lys28394PRTHuman papillomavirus 283Pro Asp Thr Thr Glu Glu Val Asp His Lys Pro Lys Leu Cys Arg Leu1 5 10 15Ala Lys Gly Glu Asn Gly Tyr Gly Phe His Leu Asn Ala Ile Arg Gly 20 25 30Leu Pro Gly Ser Phe Ile Lys Glu Val Gln Lys Gly Gly Pro Ala Asp 35 40 45Leu Ala Gly Leu Glu Asp Glu Asp Val Ile Ile Glu Val Asn Gly Val 50 55 60Asn Val Leu Asp Glu Pro Tyr Glu Lys Val Val Asp Arg Ile Gln Ser65 70 75 80Ser Gly Lys Asn Val Thr Leu Leu Val Gly Lys Asn Ser Ser 85 90284101PRTHuman papillomavirus 284Leu Thr Ser Thr Phe Asn Pro Arg Glu Cys Lys Leu Ser Lys Gln Glu1 5 10 15Gly Gln Asn Tyr Gly Phe Phe Leu Arg Ile Glu Lys Asp Thr Glu Gly 20 25 30His Leu Val Arg Val Val Glu Lys Cys Ser Pro Ala Glu Lys Ala Gly 35 40 45Leu Gln Asp Gly Asp Arg Val Leu Arg Ile Asn Gly Val Phe Val Asp 50 55 60Lys Glu Glu His Met Gln Val Val Asp Leu Val Arg Lys Ser Gly Asn65 70 75 80Ser Val Thr Leu Leu Val Leu Asp Gly Asp Ser Tyr Glu Lys Ala Gly 85 90 95Ser His Glu Pro Ser 10028599PRTHuman papillomavirus 285Leu Gly Ile Pro Thr Val Pro Gly Lys Val Thr Leu Gln Lys Asp Ala1 5 10 15Gln Asn Leu Ile Gly Ile Ser Ile Gly Gly Gly Ala Gln Tyr Cys Pro 20 25 30Cys Leu Tyr Ile Val Gln Val Phe Asp Asn Thr Pro Ala Ala Leu Asp 35 40 45Gly Thr Val Ala Ala Gly Asp Glu Ile Thr Gly Val Asn Gly Arg Ser 50 55 60Ile Lys Gly Lys Thr Lys Val Glu Val Ala Lys Met Ile Gln Glu Val65 70 75 80Lys Gly Glu Val Thr Ile His Tyr Asn Lys Leu Gln Ala Asp Pro Lys 85 90 95Gln Gly Met28698PRTHuman papillomavirus 286Ser Gln Gly Val Gly Pro Ile Arg Lys Val Leu Leu Leu Lys Glu Asp1 5 10 15His Glu Gly Leu Gly Ile Ser Ile Thr Gly Gly Lys Glu His Gly Val 20 25 30Pro Ile Leu Ile Ser Glu Ile His Pro Gly Gln Pro Ala Asp Arg Cys 35 40 45Gly Gly Leu His Val Gly Asp Ala Ile Leu Ala Val Asn Gly Val Asn 50 55 60Leu Arg Asp Thr Lys His Lys Glu Ala Val Thr Ile Leu Ser Gln Gln65 70 75 80Arg Gly Glu Ile Glu Phe Glu Val Val Tyr Val Ala Pro Glu Val Asp 85 90 95Ser Asp28798PRTHuman papillomavirus 287Thr Ala Glu Ala Thr Val Cys Thr Val Thr Leu Glu Lys Met Ser Ala1 5 10 15Gly Leu Gly Phe Ser Leu Glu Gly Gly Lys Gly Ser Leu His Gly Asp 20 25 30Lys Pro Leu Thr Ile Asn Arg Ile Phe Lys Gly Ala Ala Ser Glu Gln 35 40 45Ser Glu Thr Val Gln Pro Gly Asp Glu Ile Leu Gln Leu Gly Gly Thr 50 55 60Ala Met Gln Gly Leu Thr Arg Phe Glu Ala Trp Asn Ile Ile Lys Ala65 70 75 80Leu Pro Asp Gly Pro Val Thr Ile Val Ile Arg Arg Lys Ser Leu Gln 85 90 95Ser Lys28897PRTHuman papillomavirus 288Ile His Val Thr Ile Leu His Lys Glu Glu Gly Ala Gly Leu Gly Phe1 5 10 15Ser Leu Ala Gly Gly Ala Asp Leu Glu Asn Lys Val Ile Thr Val His 20 25 30Arg Val Phe Pro Asn Gly Leu Ala Ser Gln Glu Gly Thr Ile Gln Lys 35 40 45Gly Asn Glu Val Leu Ser Ile Asn Gly Lys Ser Leu Lys Gly Thr Thr 50 55 60His His Asp Ala Leu Ala Ile Leu Arg Gln Ala Arg Glu Pro Arg Gln65 70 75 80Ala Val Ile Val Thr Arg Lys Leu Thr Pro Glu Glu Phe Ile Val Thr 85 90 95Asp289214PRTHuman papillomavirus 289Ile His Val Thr Ile Leu His Lys Glu Glu Gly Ala Gly Leu Gly Phe1 5 10 15Ser Leu Ala Gly Gly Ala Asp Leu Glu Asn Lys Val Ile Thr Val His 20 25 30Arg Val Phe Pro Asn Gly Leu Ala Ser Gln Glu Gly Thr Ile Gln Lys 35 40 45Gly Asn Glu Val Leu Ser Ile Asn Gly Lys Ser Leu Lys Gly Thr Thr 50 55 60His His Asp Ala Leu Ala Ile Leu Arg Gln Ala Arg Glu Pro Arg Gln65 70 75 80Ala Val Ile Val Thr Arg Lys Leu Thr Pro Glu Ala Met Pro Asp Leu 85 90 95Asn Ser Ser Thr Asp Ser Ala Ala Ser Ala Ser Ala Ala Ser Asp Val 100 105 110Ser Val Glu Ser Thr Ala Glu Ala Thr Val Cys Thr Val Thr Leu Glu 115 120 125Lys Met Ser Ala Gly Leu Gly Phe Ser Leu Glu Gly Gly Lys Gly Ser 130 135 140Leu His Gly Asp Lys Pro Leu Thr Ile Asn Arg Ile Phe Lys Gly Ala145 150 155 160Ala Ser Glu Gln Ser Glu Thr Val Gln Pro Gly Asp Glu Ile Leu Gln 165 170 175Leu Gly Gly Thr Ala Met Gln Gly Leu Thr Arg Phe Glu Ala Trp Asn

180 185 190Ile Ile Lys Ala Leu Pro Asp Gly Pro Val Thr Ile Val Ile Arg Arg 195 200 205Lys Ser Leu Gln Ser Lys 210290162PRTHuman papillomavirus 290Ile Arg Glu Ala Lys Tyr Ser Gly Val Leu Ser Ser Ile Gly Lys Ile1 5 10 15Phe Lys Glu Glu Gly Leu Leu Gly Phe Phe Val Gly Leu Ile Pro His 20 25 30Leu Leu Gly Asp Val Val Phe Leu Trp Gly Cys Asn Leu Leu Ala His 35 40 45Phe Ile Asn Ala Tyr Leu Val Asp Asp Ser Val Ser Asp Thr Pro Gly 50 55 60Gly Leu Gly Asn Asp Gln Asn Pro Gly Ser Gln Phe Ser Gln Ala Leu65 70 75 80Ala Ile Arg Ser Tyr Thr Lys Phe Val Met Gly Ile Ala Val Ser Met 85 90 95Leu Thr Tyr Pro Phe Leu Leu Val Gly Asp Leu Met Ala Val Asn Asn 100 105 110Cys Gly Leu Gln Ala Gly Leu Pro Pro Tyr Ser Pro Val Phe Lys Ser 115 120 125Trp Ile His Cys Trp Lys Tyr Leu Ser Val Gln Gly Gln Leu Phe Arg 130 135 140Gly Ser Ser Leu Leu Phe Arg Arg Val Ser Ser Gly Ser Cys Phe Ala145 150 155 160Leu Glu291338PRTHuman papillomavirus 291Glu Gly Glu Met Glu Tyr Glu Glu Ile Thr Leu Glu Arg Gly Asn Ser1 5 10 15Gly Leu Gly Phe Ser Ile Ala Gly Gly Thr Asp Asn Pro His Ile Gly 20 25 30Asp Asp Pro Ser Ile Phe Ile Thr Lys Ile Ile Pro Gly Gly Ala Ala 35 40 45Ala Gln Asp Gly Arg Leu Arg Val Asn Asp Ser Ile Leu Phe Val Asn 50 55 60Glu Val Asp Val Arg Glu Val Thr His Ser Ala Ala Val Glu Ala Leu65 70 75 80Lys Glu Ala Gly Ser Ile Val Arg Leu Tyr Val Met Arg Arg Lys Pro 85 90 95Pro Ala Glu Lys Val Met Glu Ile Lys Leu Ile Lys Gly Pro Lys Gly 100 105 110Leu Gly Phe Ser Ile Ala Gly Gly Val Gly Asn Gln His Ile Pro Gly 115 120 125Asp Asn Ser Ile Tyr Val Thr Lys Ile Ile Glu Gly Gly Ala Ala His 130 135 140Lys Asp Gly Arg Leu Gln Ile Gly Asp Lys Ile Leu Ala Val Asn Ser145 150 155 160Val Gly Leu Glu Asp Val Met His Glu Asp Ala Val Ala Ala Leu Lys 165 170 175Asn Thr Tyr Asp Val Val Tyr Leu Lys Val Ala Lys Pro Ser Asn Ala 180 185 190Tyr Leu Ser Asp Ser Tyr Ala Pro Pro Asp Ile Thr Thr Ser Tyr Ser 195 200 205Gln His Leu Asp Asn Glu Ile Ser His Ser Ser Tyr Leu Gly Thr Asp 210 215 220Tyr Pro Thr Ala Met Thr Pro Thr Ser Pro Arg Arg Tyr Ser Pro Val225 230 235 240Ala Lys Asp Leu Leu Gly Glu Glu Asp Ile Pro Arg Glu Pro Arg Arg 245 250 255Ile Val Ile His Arg Gly Ser Thr Gly Leu Gly Phe Asn Ile Val Gly 260 265 270Gly Glu Asp Gly Glu Gly Ile Phe Ile Ser Phe Ile Leu Ala Gly Gly 275 280 285Pro Ala Asp Leu Ser Gly Glu Leu Arg Lys Gly Asp Gln Ile Leu Ser 290 295 300Val Asn Gly Val Asp Leu Arg Asn Ala Ser His Glu Gln Ala Ala Ile305 310 315 320Ala Leu Lys Asn Ala Gly Gln Thr Val Thr Ile Ile Ala Gln Tyr Lys 325 330 335Pro Glu 292105PRTHuman papillomavirus 292His Val Met Arg Arg Lys Pro Pro Ala Glu Lys Val Met Glu Ile Lys1 5 10 15Leu Ile Lys Gly Pro Lys Gly Leu Gly Phe Ser Ile Ala Gly Gly Val 20 25 30Gly Asn Gln His Ile Pro Gly Asp Asn Ser Ile Tyr Val Thr Lys Ile 35 40 45Ile Glu Gly Gly Ala Ala His Lys Asp Gly Arg Leu Gln Ile Gly Asp 50 55 60Lys Ile Leu Ala Val Asn Ser Val Gly Leu Glu Asp Val Met His Glu65 70 75 80Asp Ala Val Ala Ala Leu Lys Asn Thr Tyr Asp Val Val Tyr Leu Lys 85 90 95Val Ala Lys Pro Ser Asn Ala Tyr Leu 100 10529397PRTHuman papillomavirus 293Arg Glu Asp Ile Pro Arg Glu Pro Arg Arg Ile Val Ile His Arg Gly1 5 10 15Ser Thr Gly Leu Gly Phe Asn Ile Val Gly Gly Glu Asp Gly Glu Gly 20 25 30Ile Phe Ile Ser Phe Ile Leu Ala Gly Gly Pro Ala Asp Leu Ser Gly 35 40 45Glu Leu Arg Lys Gly Asp Gln Ile Leu Ser Val Asn Gly Val Asp Leu 50 55 60Arg Asn Ala Ser His Glu Gln Ala Ala Ile Ala Leu Lys Asn Ala Gly65 70 75 80Gln Thr Val Thr Ile Ile Ala Gln Tyr Lys Pro Glu Phe Ile Val Thr 85 90 95Asp29499PRTHuman papillomavirus 294Leu Glu Tyr Glu Glu Ile Thr Leu Glu Arg Gly Asn Ser Gly Leu Gly1 5 10 15Phe Ser Ile Ala Gly Gly Thr Asp Asn Pro His Ile Gly Asp Asp Pro 20 25 30Ser Ile Phe Ile Thr Lys Ile Ile Pro Gly Gly Ala Ala Ala Gln Asp 35 40 45Gly Arg Leu Arg Val Asn Asp Ser Ile Leu Phe Val Asn Glu Val Asp 50 55 60Val Arg Glu Val Thr His Ser Ala Ala Val Glu Ala Leu Lys Glu Ala65 70 75 80Gly Ser Ile Val Arg Leu Tyr Val Met Arg Arg Lys Pro Pro Ala Glu 85 90 95Asn Ser Ser29588PRTHuman papillomavirus 295Arg Asp Met Ala Glu Ala His Lys Glu Ala Met Ser Arg Lys Leu Gly1 5 10 15Gln Ser Glu Ser Gln Gly Pro Pro Arg Ala Phe Ala Lys Val Asn Ser 20 25 30Ile Ser Pro Gly Ser Pro Ala Ser Ile Ala Gly Leu Gln Val Asp Asp 35 40 45Glu Ile Val Glu Phe Gly Ser Val Asn Thr Gln Asn Phe Gln Ser Leu 50 55 60His Asn Ile Gly Ser Val Val Gln His Ser Glu Gly Ala Leu Ala Pro65 70 75 80Thr Ile Leu Leu Ser Val Ser Met 85296102PRTHuman papillomavirus 296Gln Asn Asp Asn Gly Asp Ser Tyr Leu Val Leu Ile Arg Ile Thr Pro1 5 10 15Asp Glu Asp Gly Lys Phe Gly Phe Asn Leu Lys Gly Gly Val Asp Gln 20 25 30Lys Met Pro Leu Val Val Ser Arg Ile Asn Pro Glu Ser Pro Ala Asp 35 40 45Thr Cys Ile Pro Lys Leu Asn Glu Gly Asp Gln Ile Val Leu Ile Asn 50 55 60Gly Arg Asp Ile Ser Glu His Thr His Asp Gln Val Val Met Phe Ile65 70 75 80Lys Ala Ser Arg Glu Ser His Ser Arg Glu Leu Ala Leu Val Ile Arg 85 90 95Arg Arg Ala Val Arg Ser 10029788PRTHuman papillomavirus 297Ile Arg Met Lys Pro Asp Glu Asn Gly Arg Phe Gly Phe Asn Val Lys1 5 10 15Gly Gly Tyr Asp Gln Lys Met Pro Val Ile Val Ser Arg Val Ala Pro 20 25 30Gly Thr Pro Ala Asp Leu Cys Val Pro Arg Leu Asn Glu Gly Asp Gln 35 40 45Val Val Leu Ile Asn Gly Arg Asp Ile Ala Glu His Thr His Asp Gln 50 55 60Val Val Leu Phe Ile Lys Ala Ser Cys Glu Arg His Ser Gly Glu Leu65 70 75 80Met Leu Leu Val Arg Pro Asn Ala 8529895PRTHuman papillomavirus 298Gly Asp Ile Phe Glu Val Glu Leu Ala Lys Asn Asp Asn Ser Leu Gly1 5 10 15Ile Ser Val Thr Gly Gly Val Asn Thr Ser Val Arg His Gly Gly Ile 20 25 30Tyr Val Lys Ala Val Ile Pro Gln Gly Ala Ala Glu Ser Asp Gly Arg 35 40 45Ile His Lys Gly Asp Arg Val Leu Ala Val Asn Gly Val Ser Leu Glu 50 55 60Gly Ala Thr His Lys Gln Ala Val Glu Thr Leu Arg Asn Thr Gly Gln65 70 75 80Val Val His Leu Leu Leu Glu Lys Gly Gln Ser Pro Thr Ser Lys 85 90 95299106PRTHuman papillomavirus 299Pro Glu Arg Glu Ile Thr Leu Val Asn Leu Lys Lys Asp Ala Lys Tyr1 5 10 15Gly Leu Gly Phe Gln Ile Ile Gly Gly Glu Lys Met Gly Arg Leu Asp 20 25 30Leu Gly Ile Phe Ile Ser Ser Val Ala Pro Gly Gly Pro Ala Asp Phe 35 40 45His Gly Cys Leu Lys Pro Gly Asp Arg Leu Ile Ser Val Asn Ser Val 50 55 60Ser Leu Glu Gly Val Ser His His Ala Ala Ile Glu Ile Leu Gln Asn65 70 75 80Ala Pro Glu Asp Val Thr Leu Val Ile Ser Gln Pro Lys Glu Lys Ile 85 90 95Ser Lys Val Pro Ser Thr Pro Val His Leu 100 10530098PRTHuman papillomavirus 300Glu Leu Glu Val Glu Leu Leu Ile Thr Leu Ile Lys Ser Glu Lys Ala1 5 10 15Ser Leu Gly Phe Thr Val Thr Lys Gly Asn Gln Arg Ile Gly Cys Tyr 20 25 30Val His Asp Val Ile Gln Asp Pro Ala Lys Ser Asp Gly Arg Leu Lys 35 40 45Pro Gly Asp Arg Leu Ile Lys Val Asn Asp Thr Asp Val Thr Asn Met 50 55 60Thr His Thr Asp Ala Val Asn Leu Leu Arg Ala Ala Ser Lys Thr Val65 70 75 80Arg Leu Val Ile Gly Arg Val Leu Glu Leu Pro Arg Ile Pro Met Leu 85 90 95Pro His301104PRTHuman papillomavirus 301Thr Glu Glu Asn Thr Phe Glu Val Lys Leu Phe Lys Asn Ser Ser Gly1 5 10 15Leu Gly Phe Ser Phe Ser Arg Glu Asp Asn Leu Ile Pro Glu Gln Ile 20 25 30Asn Ala Ser Ile Val Arg Val Lys Lys Leu Phe Ala Gly Gln Pro Ala 35 40 45Ala Glu Ser Gly Lys Ile Asp Val Gly Asp Val Ile Leu Lys Val Asn 50 55 60Gly Ala Ser Leu Lys Gly Leu Ser Gln Gln Glu Val Ile Ser Ala Leu65 70 75 80Arg Gly Thr Ala Pro Glu Val Phe Leu Leu Leu Cys Arg Pro Pro Pro 85 90 95Gly Val Leu Pro Glu Ile Asp Thr 10030294PRTHuman papillomavirus 302Met Leu Pro His Leu Leu Pro Asp Ile Thr Leu Thr Cys Asn Lys Glu1 5 10 15Glu Leu Gly Phe Ser Leu Cys Gly Gly His Asp Ser Leu Tyr Gln Val 20 25 30Val Tyr Ile Ser Asp Ile Asn Pro Arg Ser Val Ala Ala Ile Glu Gly 35 40 45Asn Leu Gln Leu Leu Asp Val Ile His Tyr Val Asn Gly Val Ser Thr 50 55 60Gln Gly Met Thr Leu Glu Glu Val Asn Arg Ala Leu Asp Met Ser Leu65 70 75 80Pro Ser Leu Val Leu Lys Ala Thr Arg Asn Asp Leu Pro Val 85 9030392PRTHuman papillomavirus 303Val Cys Ser Glu Arg Arg Tyr Arg Gln Ile Thr Ile Pro Arg Gly Lys1 5 10 15Asp Gly Phe Gly Phe Thr Ile Cys Cys Asp Ser Pro Val Arg Val Gln 20 25 30Ala Val Asp Ser Gly Gly Pro Ala Glu Arg Ala Gly Leu Gln Gln Leu 35 40 45Asp Thr Val Leu Gln Leu Asn Glu Arg Pro Val Glu His Trp Lys Cys 50 55 60Val Glu Leu Ala His Glu Ile Arg Ser Cys Pro Ser Glu Ile Ile Leu65 70 75 80Leu Val Trp Arg Met Val Pro Gln Val Lys Pro Gly 85 9030493PRTHuman papillomavirus 304Arg Pro Ser Pro Pro Arg Val Arg Ser Val Glu Val Ala Arg Gly Arg1 5 10 15Ala Gly Tyr Gly Phe Thr Leu Ser Gly Gln Ala Pro Cys Val Leu Ser 20 25 30Cys Val Met Arg Gly Ser Pro Ala Asp Phe Val Gly Leu Arg Ala Gly 35 40 45Asp Gln Ile Leu Ala Val Asn Glu Ile Asn Val Lys Lys Ala Ser His 50 55 60Glu Asp Val Val Lys Leu Ile Gly Lys Cys Ser Gly Val Leu His Met65 70 75 80Val Ile Ala Glu Gly Val Gly Arg Phe Glu Ser Cys Ser 85 90305124PRTHuman papillomavirus 305Ser Glu Asp Glu Thr Phe Ser Trp Pro Gly Pro Lys Thr Val Thr Leu1 5 10 15Lys Arg Thr Ser Gln Gly Phe Gly Phe Thr Leu Arg His Phe Ile Val 20 25 30Tyr Pro Pro Glu Ser Ala Ile Gln Phe Ser Tyr Lys Asp Glu Glu Asn 35 40 45Gly Asn Arg Gly Gly Lys Gln Arg Asn Arg Leu Glu Pro Met Asp Thr 50 55 60Ile Phe Val Lys Gln Val Lys Glu Gly Gly Pro Ala Phe Glu Ala Gly65 70 75 80Leu Cys Thr Gly Asp Arg Ile Ile Lys Val Asn Gly Glu Ser Val Ile 85 90 95Gly Lys Thr Tyr Ser Gln Val Ile Ala Leu Ile Gln Asn Ser Asp Thr 100 105 110Thr Leu Glu Leu Ser Val Met Pro Lys Asp Glu Asp 115 12030696PRTHuman papillomavirus 306Ser Ala Lys Asn Arg Trp Arg Leu Val Gly Pro Val His Leu Thr Arg1 5 10 15Gly Glu Gly Gly Phe Gly Leu Thr Leu Arg Gly Asp Ser Pro Val Leu 20 25 30Ile Ala Ala Val Ile Pro Gly Ser Gln Ala Ala Ala Ala Gly Leu Lys 35 40 45Glu Gly Asp Tyr Ile Val Ser Val Asn Gly Gln Pro Cys Arg Trp Trp 50 55 60Arg His Ala Glu Val Val Thr Glu Leu Lys Ala Ala Gly Glu Ala Gly65 70 75 80Ala Ser Leu Gln Val Val Ser Leu Leu Pro Ser Ser Arg Leu Pro Ser 85 90 95307104PRTHuman papillomavirus 307Ile Ser Phe Ser Ala Asn Lys Arg Trp Thr Pro Pro Arg Ser Ile Arg1 5 10 15Phe Thr Ala Glu Glu Gly Asp Leu Gly Phe Thr Leu Arg Gly Asn Ala 20 25 30Pro Val Gln Val His Phe Leu Asp Pro Tyr Cys Ser Ala Ser Val Ala 35 40 45Gly Ala Arg Glu Gly Asp Tyr Ile Val Ser Ile Gln Leu Val Asp Cys 50 55 60Lys Trp Leu Thr Leu Ser Glu Val Met Lys Leu Leu Lys Ser Phe Gly65 70 75 80Glu Asp Glu Ile Glu Met Lys Val Val Ser Leu Leu Asp Ser Thr Ser 85 90 95Ser Met His Asn Lys Ser Ala Thr 100308126PRTHuman papillomavirus 308Thr Leu Asn Glu Glu His Ser His Ser Asp Lys His Pro Val Thr Trp1 5 10 15Gln Pro Ser Lys Asp Gly Asp Arg Leu Ile Gly Arg Ile Leu Leu Asn 20 25 30Lys Arg Leu Lys Asp Gly Ser Val Pro Arg Asp Ser Gly Ala Met Leu 35 40 45Gly Leu Lys Val Val Gly Gly Lys Met Thr Glu Ser Gly Arg Leu Cys 50 55 60Ala Phe Ile Thr Lys Val Lys Lys Gly Ser Leu Ala Asp Thr Val Gly65 70 75 80His Leu Arg Pro Gly Asp Glu Val Leu Glu Trp Asn Gly Arg Leu Leu 85 90 95Gln Gly Ala Thr Phe Glu Glu Val Tyr Asn Ile Ile Leu Glu Ser Lys 100 105 110Pro Glu Pro Gln Val Glu Leu Val Val Ser Arg Pro Ile Gly 115 120 125309101PRTHuman papillomavirus 309Gln Glu Met Asp Arg Glu Glu Leu Glu Leu Glu Glu Val Asp Leu Tyr1 5 10 15Arg Met Asn Ser Gln Asp Lys Leu Gly Leu Thr Val Cys Tyr Arg Thr 20 25 30Asp Asp Glu Asp Asp Ile Gly Ile Tyr Ile Ser Glu Ile Asp Pro Asn 35 40 45Ser Ile Ala Ala Lys Asp Gly Arg Ile Arg Glu Gly Asp Arg Ile Ile 50 55 60Gln Ile Asn Gly Ile Glu Val Gln Asn Arg Glu Glu Ala Val Ala Leu65 70 75 80Leu Thr Ser Glu Glu Asn Lys Asn Phe Ser Leu Leu Ile Ala Arg Pro 85 90 95Glu Leu Gln Leu Asp 100310107PRTHuman papillomavirus 310Gln Gly Glu Glu Thr Lys Ser Leu Thr Leu Val Leu His Arg Asp Ser1 5 10 15Gly Ser Leu Gly Phe Asn Ile Ile Gly Gly Arg Pro Ser Val Asp Asn 20 25 30His Asp Gly Ser Ser Ser Glu Gly Ile Phe Val Ser Lys Ile Val Asp 35 40 45Ser Gly Pro Ala Ala Lys Glu Gly Gly Leu Gln Ile His Asp Arg Ile 50 55 60Ile Glu Val

Asn Gly Arg Asp Leu Ser Arg Ala Thr His Asp Gln Ala65 70 75 80Val Glu Ala Phe Lys Thr Ala Lys Glu Pro Ile Val Val Gln Val Leu 85 90 95Arg Arg Thr Pro Arg Thr Lys Met Phe Thr Pro 100 10531198PRTHuman papillomavirus 311Ile Leu Ala His Val Lys Gly Ile Glu Lys Glu Val Asn Val Tyr Lys1 5 10 15Ser Glu Asp Ser Leu Gly Leu Thr Ile Thr Asp Asn Gly Val Gly Tyr 20 25 30 Ala Phe Ile Lys Arg Ile Lys Asp Gly Gly Val Ile Asp Ser Val Lys 35 40 45 Thr Ile Cys Val Gly Asp His Ile Glu Ser Ile Asn Gly Glu Asn Ile 50 55 60 Val Gly Trp Arg His Tyr Asp Val Ala Lys Lys Leu Lys Glu Leu Lys65 70 75 80Lys Glu Glu Leu Phe Thr Met Lys Leu Ile Glu Pro Lys Lys Ala Phe 85 90 95Glu Ile312109PRTHuman papillomavirus 312Arg Gly Glu Lys Lys Asn Ser Ser Ser Gly Ile Ser Gly Ser Gln Arg1 5 10 15Arg Tyr Ile Gly Val Met Met Leu Thr Leu Ser Pro Ser Ile Leu Ala 20 25 30Glu Leu Gln Leu Arg Glu Pro Ser Phe Pro Asp Val Gln His Gly Val 35 40 45Leu Ile His Lys Val Ile Leu Gly Ser Pro Ala His Arg Ala Gly Leu 50 55 60Arg Pro Gly Asp Val Ile Leu Ala Ile Gly Glu Gln Met Val Gln Asn65 70 75 80Ala Glu Asp Val Tyr Glu Ala Val Arg Thr Gln Ser Gln Leu Ala Val 85 90 95Gln Ile Arg Arg Gly Arg Glu Thr Leu Thr Leu Tyr Val 100 105313110PRTHuman papillomavirus 313Ile Leu Glu Glu Lys Thr Val Val Leu Gln Lys Lys Asp Asn Glu Gly1 5 10 15Phe Gly Phe Val Leu Arg Gly Ala Lys Ala Asp Thr Pro Ile Glu Glu 20 25 30Phe Thr Pro Thr Pro Ala Phe Pro Ala Leu Gln Tyr Leu Glu Ser Val 35 40 45Asp Glu Gly Gly Val Ala Trp Gln Ala Gly Leu Arg Thr Gly Asp Phe 50 55 60Leu Ile Glu Val Asn Asn Glu Asn Val Val Lys Val Gly His Arg Gln65 70 75 80Val Val Asn Met Ile Arg Gln Gly Gly Asn His Leu Val Leu Lys Val 85 90 95Val Thr Val Thr Arg Asn Leu Asp Pro Asp Asp Asn Ser Ser 100 105 110314113PRTHuman papillomavirus 314Ile Leu Lys Glu Lys Thr Val Leu Leu Gln Lys Lys Asp Ser Glu Gly1 5 10 15Phe Gly Phe Val Leu Arg Gly Ala Lys Ala Gln Thr Pro Ile Glu Glu 20 25 30Phe Thr Pro Thr Pro Ala Phe Pro Ala Leu Gln Tyr Leu Glu Ser Val 35 40 45Asp Glu Gly Gly Val Ala Trp Arg Ala Gly Leu Arg Met Gly Asp Phe 50 55 60Leu Ile Glu Val Asn Gly Gln Asn Val Val Lys Val Gly His Arg Gln65 70 75 80Val Val Asn Met Ile Arg Gln Gly Gly Asn Thr Leu Met Val Lys Val 85 90 95Val Met Val Thr Arg His Pro Asp Met Asp Glu Ala Val Gln Asn Ser 100 105 110Ser315110PRTHuman papillomavirus 315Ser Asp Tyr Val Ile Asp Asp Lys Val Ala Val Leu Gln Lys Arg Asp1 5 10 15His Glu Gly Phe Gly Phe Val Leu Arg Gly Ala Lys Ala Glu Thr Pro 20 25 30Ile Glu Glu Phe Thr Pro Thr Pro Ala Phe Pro Ala Leu Gln Tyr Leu 35 40 45Glu Ser Val Asp Val Glu Gly Val Ala Trp Arg Ala Gly Leu Arg Thr 50 55 60Gly Asp Phe Leu Ile Glu Val Asn Gly Val Asn Val Val Lys Val Gly65 70 75 80His Lys Gln Val Val Ala Leu Ile Arg Gln Gly Gly Asn Arg Leu Val 85 90 95Met Lys Val Val Ser Val Thr Arg Lys Pro Glu Glu Asp Gly 100 105 11031698PRTHuman papillomavirus 316Ser Asn Ser Pro Arg Glu Glu Ile Phe Gln Val Ala Leu His Lys Arg1 5 10 15Asp Ser Gly Glu Gln Leu Gly Ile Lys Leu Val Arg Arg Thr Asp Glu 20 25 30Pro Gly Val Phe Ile Leu Asp Leu Leu Glu Gly Gly Leu Ala Ala Gln 35 40 45Asp Gly Arg Leu Ser Ser Asn Asp Arg Val Leu Ala Ile Asn Gly His 50 55 60Asp Leu Lys Tyr Gly Thr Pro Glu Leu Ala Ala Gln Ile Ile Gln Ala65 70 75 80Ser Gly Glu Arg Val Asn Leu Thr Ile Ala Arg Pro Gly Lys Pro Gln 85 90 95Pro Gly317104PRTHuman papillomavirus 317Ile Gln Cys Val Thr Cys Gln Glu Lys His Ile Thr Val Lys Lys Glu1 5 10 15Pro His Glu Ser Leu Gly Met Thr Val Ala Gly Gly Arg Gly Ser Lys 20 25 30Ser Gly Glu Leu Pro Ile Phe Val Thr Ser Val Pro Pro His Gly Cys 35 40 45Leu Ala Arg Asp Gly Arg Ile Lys Arg Gly Asp Val Leu Leu Asn Ile 50 55 60Asn Gly Ile Asp Leu Thr Asn Leu Ser His Ser Glu Ala Val Ala Met65 70 75 80Leu Lys Ala Ser Ala Ala Ser Pro Ala Val Ala Leu Lys Ala Leu Glu 85 90 95Val Gln Ile Val Glu Glu Ala Thr 100318110PRTHuman papillomavirus 318Met Gly Leu Gly Val Ser Ala Glu Gln Pro Ala Gly Gly Ala Glu Gly1 5 10 15Phe His Leu His Gly Val Gln Glu Asn Ser Pro Ala Gln Gln Ala Gly 20 25 30Leu Glu Pro Tyr Phe Asp Phe Ile Ile Thr Ile Gly His Ser Arg Leu 35 40 45Asn Lys Glu Asn Asp Thr Leu Lys Ala Leu Leu Lys Ala Asn Val Glu 50 55 60Lys Pro Val Lys Leu Glu Val Phe Asn Met Lys Thr Met Arg Val Arg65 70 75 80Glu Val Glu Val Val Pro Ser Asn Met Trp Gly Gly Gln Gly Leu Leu 85 90 95Gly Ala Ser Val Arg Phe Cys Ser Phe Arg Arg Ala Ser Glu 100 105 110319109PRTHuman papillomavirus 319Arg Ala Ser Glu Gln Val Trp His Val Leu Asp Val Glu Pro Ser Ser1 5 10 15Pro Ala Ala Leu Ala Gly Leu Arg Pro Tyr Thr Asp Tyr Val Val Gly 20 25 30Ser Asp Gln Ile Leu Gln Glu Ser Glu Asp Phe Phe Thr Leu Ile Glu 35 40 45Ser His Glu Gly Lys Pro Leu Lys Leu Met Val Tyr Asn Ser Lys Ser 50 55 60Asp Ser Cys Arg Glu Ser Gly Met Trp His Trp Leu Trp Val Ser Thr65 70 75 80Pro Asp Pro Asn Ser Ala Pro Gln Leu Pro Gln Glu Ala Thr Trp His 85 90 95Pro Thr Thr Phe Cys Ser Thr Thr Trp Cys Pro Thr Thr 100 105320101PRTHuman papillomavirus 320Ile Ser Val Thr Asp Gly Pro Lys Phe Glu Val Lys Leu Lys Lys Asn1 5 10 15Ala Asn Gly Leu Gly Phe Ser Phe Val Gln Met Glu Lys Glu Ser Cys 20 25 30Ser His Leu Lys Ser Asp Leu Val Arg Ile Lys Arg Leu Phe Pro Gly 35 40 45Gln Pro Ala Glu Glu Asn Gly Ala Ile Ala Ala Gly Asp Ile Ile Leu 50 55 60Ala Val Asn Gly Arg Ser Thr Glu Gly Leu Ile Phe Gln Glu Val Leu65 70 75 80His Leu Leu Arg Gly Ala Pro Gln Glu Val Thr Leu Leu Leu Cys Arg 85 90 95Pro Pro Pro Gly Ala 100321100PRTHuman papillomavirus 321Gln Pro Glu Pro Leu Arg Pro Arg Leu Cys Arg Leu Val Arg Gly Glu1 5 10 15Gln Gly Tyr Gly Phe His Leu His Gly Glu Lys Gly Arg Arg Gly Gln 20 25 30Phe Ile Arg Arg Val Glu Pro Gly Ser Pro Ala Glu Ala Ala Ala Leu 35 40 45Arg Ala Gly Asp Arg Leu Val Glu Val Asn Gly Val Asn Val Glu Gly 50 55 60Glu Thr His His Gln Val Val Gln Arg Ile Lys Ala Val Glu Gly Gln65 70 75 80Thr Arg Leu Leu Val Val Asp Gln Glu Thr Asp Glu Glu Leu Arg Arg 85 90 95Arg Asn Ser Ser 10032299PRTHuman papillomavirus 322Pro Leu Arg Glu Leu Arg Pro Arg Leu Cys His Leu Arg Lys Gly Pro1 5 10 15Gln Gly Tyr Gly Phe Asn Leu His Ser Asp Lys Ser Arg Pro Gly Gln 20 25 30Tyr Ile Arg Ser Val Asp Pro Gly Ser Pro Ala Ala Arg Ser Gly Leu 35 40 45Arg Ala Gln Asp Arg Leu Ile Glu Val Asn Gly Gln Asn Val Glu Gly 50 55 60Leu Arg His Ala Glu Val Val Ala Ser Ile Lys Ala Arg Glu Asp Glu65 70 75 80Ala Arg Leu Leu Val Val Asp Pro Glu Thr Asp Glu His Phe Lys Arg 85 90 95Asn Ser Ser32392PRTHuman papillomavirus 323Pro Gly Val Arg Glu Ile His Leu Cys Lys Asp Glu Arg Gly Lys Thr1 5 10 15Gly Leu Arg Leu Arg Lys Val Asp Gln Gly Leu Phe Val Gln Leu Val 20 25 30Gln Ala Asn Thr Pro Ala Ser Leu Val Gly Leu Arg Phe Gly Asp Gln 35 40 45Leu Leu Gln Ile Asp Gly Arg Asp Cys Ala Gly Trp Ser Ser His Lys 50 55 60Ala His Gln Val Val Lys Lys Ala Ser Gly Asp Lys Ile Val Val Val65 70 75 80Val Arg Asp Arg Pro Phe Gln Arg Thr Val Thr Met 85 9032490PRTHuman papillomavirus 324Pro Phe Gln Arg Thr Val Thr Met His Lys Asp Ser Met Gly His Val1 5 10 15Gly Phe Val Ile Lys Lys Gly Lys Ile Val Ser Leu Val Lys Gly Ser 20 25 30Ser Ala Ala Arg Asn Gly Leu Leu Thr Asn His Tyr Val Cys Glu Val 35 40 45Asp Gly Gln Asn Val Ile Gly Leu Lys Asp Lys Lys Ile Met Glu Ile 50 55 60Leu Ala Thr Ala Gly Asn Val Val Thr Leu Thr Ile Ile Pro Ser Val65 70 75 80Ile Tyr Glu His Ile Val Glu Phe Ile Val 85 9032596PRTHuman papillomavirus 325Ser Leu Glu Arg Pro Arg Phe Cys Leu Leu Ser Lys Glu Glu Gly Lys1 5 10 15Ser Phe Gly Phe His Leu Gln Gln Glu Leu Gly Arg Ala Gly His Val 20 25 30Val Cys Arg Val Asp Pro Gly Thr Ser Ala Gln Arg Gln Gly Leu Gln 35 40 45Glu Gly Asp Arg Ile Leu Ala Val Asn Asn Asp Val Val Glu His Glu 50 55 60Asp Tyr Ala Val Val Val Arg Arg Ile Arg Ala Ser Ser Pro Arg Val65 70 75 80Leu Leu Thr Val Leu Ala Arg His Ala His Asp Val Ala Arg Ala Gln 85 90 9532692PRTHuman papillomavirus 326Leu Arg Asp Arg Pro Phe Glu Arg Thr Ile Thr Met His Lys Asp Ser1 5 10 15Thr Gly His Val Gly Phe Ile Phe Lys Asn Gly Lys Ile Thr Ser Ile 20 25 30Val Lys Asp Ser Ser Ala Ala Arg Asn Gly Leu Leu Thr Glu His Asn 35 40 45Ile Cys Glu Ile Asn Gly Gln Asn Val Ile Gly Leu Lys Asp Ser Gln 50 55 60Ile Ala Asp Ile Leu Ser Thr Ser Gly Thr Val Val Thr Ile Thr Ile65 70 75 80Met Pro Ala Phe Ile Phe Glu His Met Asn Ser Ser 85 9032788PRTHuman papillomavirus 327Leu Glu Ile Lys Gln Gly Ile Arg Glu Val Ile Leu Cys Lys Asp Gln1 5 10 15Asp Gly Lys Ile Gly Leu Arg Leu Lys Ser Ile Asp Asn Gly Ile Phe 20 25 30Val Gln Leu Val Gln Ala Asn Ser Pro Ala Ser Leu Val Gly Leu Arg 35 40 45Phe Gly Asp Gln Val Leu Gln Ile Asn Gly Glu Asn Cys Ala Gly Trp 50 55 60Ser Ser Asp Lys Ala His Lys Val Leu Lys Gln Ala Phe Gly Glu Lys65 70 75 80Ile Thr Met Arg Ile His Arg Asp 8532894PRTHuman papillomavirus 328Gln Arg Arg Arg Val Thr Val Arg Lys Ala Asp Ala Gly Gly Leu Gly1 5 10 15Ile Ser Ile Lys Gly Gly Arg Glu Asn Lys Met Pro Ile Leu Ile Ser 20 25 30Lys Ile Phe Lys Gly Leu Ala Ala Asp Gln Thr Glu Ala Leu Phe Val 35 40 45Gly Asp Ala Ile Leu Ser Val Asn Gly Glu Asp Leu Ser Ser Ala Thr 50 55 60His Asp Glu Ala Val Gln Val Leu Lys Lys Thr Gly Lys Glu Val Val65 70 75 80Leu Glu Val Lys Tyr Met Lys Asp Val Ser Pro Tyr Phe Lys 85 9032988PRTHuman papillomavirus 329Pro Val Arg Arg Val Arg Val Val Lys Gln Glu Ala Gly Gly Leu Gly1 5 10 15Ile Ser Ile Lys Gly Gly Arg Glu Asn Arg Met Pro Ile Leu Ile Ser 20 25 30Lys Ile Phe Pro Gly Leu Ala Ala Asp Gln Ser Arg Ala Leu Arg Leu 35 40 45Gly Asp Ala Ile Leu Ser Val Asn Gly Thr Asp Leu Arg Gln Ala Thr 50 55 60His Asp Gln Ala Val Gln Ala Leu Lys Arg Ala Gly Lys Glu Val Leu65 70 75 80Leu Glu Val Lys Phe Ile Arg Glu 85330100PRTHuman papillomavirus 330Glu Pro Phe Tyr Ser Gly Glu Arg Thr Val Thr Ile Arg Arg Gln Thr1 5 10 15Val Gly Gly Phe Gly Leu Ser Ile Lys Gly Gly Ala Glu His Asn Ile 20 25 30Pro Val Val Val Ser Lys Ile Ser Lys Glu Gln Arg Ala Glu Leu Ser 35 40 45Gly Leu Leu Phe Ile Gly Asp Ala Ile Leu Gln Ile Asn Gly Ile Asn 50 55 60Val Arg Lys Cys Arg His Glu Glu Val Val Gln Val Leu Arg Asn Ala65 70 75 80Gly Glu Glu Val Thr Leu Thr Val Ser Phe Leu Lys Arg Ala Pro Ala 85 90 95Phe Leu Lys Leu 10033199PRTHuman papillomavirus 331Ser His Gln Gly Arg Asn Arg Arg Thr Val Thr Leu Arg Arg Gln Pro1 5 10 15Val Gly Gly Leu Gly Leu Ser Ile Lys Gly Gly Ser Glu His Asn Val 20 25 30Pro Val Val Ile Ser Lys Ile Phe Glu Asp Gln Ala Ala Asp Gln Thr 35 40 45Gly Met Leu Phe Val Gly Asp Ala Val Leu Gln Val Asn Gly Ile His 50 55 60Val Glu Asn Ala Thr His Glu Glu Val Val His Leu Leu Arg Asn Ala65 70 75 80Gly Asp Glu Val Thr Ile Thr Val Glu Tyr Leu Arg Glu Ala Pro Ala 85 90 95Phe Leu Lys33291PRTHuman papillomavirus 332Arg Gly Glu Thr Lys Glu Val Glu Val Thr Lys Thr Glu Asp Ala Leu1 5 10 15Gly Leu Thr Ile Thr Asp Asn Gly Ala Gly Tyr Ala Phe Ile Lys Arg 20 25 30Ile Lys Glu Gly Ser Ile Ile Asn Arg Ile Glu Ala Val Cys Val Gly 35 40 45Asp Ser Ile Glu Ala Ile Asn Asp His Ser Ile Val Gly Cys Arg His 50 55 60Tyr Glu Val Ala Lys Met Leu Arg Glu Leu Pro Lys Ser Gln Pro Phe65 70 75 80Thr Leu Arg Leu Val Gln Pro Lys Arg Ala Phe 85 9033388PRTHuman papillomavirus 333His Ser Ile His Ile Glu Lys Ser Asp Thr Ala Ala Asp Thr Tyr Gly1 5 10 15Phe Ser Leu Ser Ser Val Glu Glu Asp Gly Ile Arg Arg Leu Tyr Val 20 25 30Asn Ser Val Lys Glu Thr Gly Leu Ala Ser Lys Lys Gly Leu Lys Ala 35 40 45Gly Asp Glu Ile Leu Glu Ile Asn Asn Arg Ala Ala Asp Ala Leu Asn 50 55 60Ser Ser Met Leu Lys Asp Phe Leu Ser Gln Pro Ser Leu Gly Leu Leu65 70 75 80Val Arg Thr Tyr Pro Glu Leu Glu 8533497PRTHuman papillomavirus 334Pro Leu Asn Val Tyr Asp Val Gln Leu Thr Lys Thr Gly Ser Val Cys1 5 10 15Asp Phe Gly Phe Ala Val Thr Ala Gln Val Asp Glu Arg Gln His Leu 20 25 30Ser Arg Ile Phe Ile Ser Asp Val Leu Pro Asp Gly Leu Ala Tyr Gly 35 40 45Glu Gly Leu Arg Lys Gly Asn Glu Ile Met Thr Leu Asn Gly Glu Ala 50 55 60Val Ser Asp Leu Asp

Leu Lys Gln Met Glu Ala Leu Phe Ser Glu Lys65 70 75 80Ser Val Gly Leu Thr Leu Ile Ala Arg Pro Pro Asp Thr Lys Ala Thr 85 90 95Leu335103PRTHuman papillomavirus 335Gln Arg Val Glu Ile His Lys Leu Arg Gln Gly Glu Asn Leu Ile Leu1 5 10 15Gly Phe Ser Ile Gly Gly Gly Ile Asp Gln Asp Pro Ser Gln Asn Pro 20 25 30Phe Ser Glu Asp Lys Thr Asp Lys Gly Ile Tyr Val Thr Arg Val Ser 35 40 45Glu Gly Gly Pro Ala Glu Ile Ala Gly Leu Gln Ile Gly Asp Lys Ile 50 55 60Met Gln Val Asn Gly Trp Asp Met Thr Met Val Thr His Asp Gln Ala65 70 75 80Arg Lys Arg Leu Thr Lys Arg Ser Glu Glu Val Val Arg Leu Leu Val 85 90 95Thr Arg Gln Ser Leu Gln Lys 10033686PRTHuman papillomavirus 336Arg Lys Glu Val Glu Val Phe Lys Ser Glu Asp Ala Leu Gly Leu Thr1 5 10 15Ile Thr Asp Asn Gly Ala Gly Tyr Ala Phe Ile Lys Arg Ile Lys Glu 20 25 30Gly Ser Val Ile Asp His Ile His Leu Ile Ser Val Gly Asp Met Ile 35 40 45Glu Ala Ile Asn Gly Gln Ser Leu Leu Gly Cys Arg His Tyr Glu Val 50 55 60Ala Arg Leu Leu Lys Glu Leu Pro Arg Gly Arg Thr Phe Thr Leu Lys65 70 75 80Leu Thr Glu Pro Arg Lys 8533791PRTHuman papillomavirus 337His Ser His Pro Arg Val Val Glu Leu Pro Lys Thr Asp Glu Gly Leu1 5 10 15Gly Phe Asn Val Met Gly Gly Lys Glu Gln Asn Ser Pro Ile Tyr Ile 20 25 30Ser Arg Ile Ile Pro Gly Gly Val Ala Glu Arg His Gly Gly Leu Lys 35 40 45Arg Gly Asp Gln Leu Leu Ser Val Asn Gly Val Ser Val Glu Gly Glu 50 55 60His His Glu Lys Ala Val Glu Leu Leu Lys Ala Ala Lys Asp Ser Val65 70 75 80Lys Leu Val Val Arg Tyr Thr Pro Lys Val Leu 85 9033897PRTHuman papillomavirus 338Leu Ser Asn Gln Lys Arg Gly Val Lys Val Leu Lys Gln Glu Leu Gly1 5 10 15Gly Leu Gly Ile Ser Ile Lys Gly Gly Lys Glu Asn Lys Met Pro Ile 20 25 30Leu Ile Ser Lys Ile Phe Lys Gly Leu Ala Ala Asp Gln Thr Gln Ala 35 40 45Leu Tyr Val Gly Asp Ala Ile Leu Ser Val Asn Gly Ala Asp Leu Arg 50 55 60Asp Ala Thr His Asp Glu Ala Val Gln Ala Leu Lys Arg Ala Gly Lys65 70 75 80Glu Val Leu Leu Glu Val Lys Tyr Met Arg Glu Ala Thr Pro Tyr Val 85 90 95Lys33998PRTHuman papillomavirus 339Ile Gln Arg Ser Ser Ile Lys Thr Val Glu Leu Ile Lys Gly Asn Leu1 5 10 15Gln Ser Val Gly Leu Thr Leu Arg Leu Val Gln Ser Thr Asp Gly Tyr 20 25 30Ala Gly His Val Ile Ile Glu Thr Val Ala Pro Asn Ser Pro Ala Ala 35 40 45Ile Ala Asp Leu Gln Arg Gly Asp Arg Leu Ile Ala Ile Gly Gly Val 50 55 60Lys Ile Thr Ser Thr Leu Gln Val Leu Lys Leu Ile Lys Gln Ala Gly65 70 75 80Asp Arg Val Leu Val Tyr Tyr Glu Arg Pro Val Gly Gln Ser Asn Gln 85 90 95Gly Ala340103PRTHuman papillomavirus 340Ile Leu Thr Leu Thr Ile Leu Arg Gln Thr Gly Gly Leu Gly Ile Ser1 5 10 15Ile Ala Gly Gly Lys Gly Ser Thr Pro Tyr Lys Gly Asp Asp Glu Gly 20 25 30Ile Phe Ile Ser Arg Val Ser Glu Glu Gly Pro Ala Ala Arg Ala Gly 35 40 45Val Arg Val Gly Asp Lys Leu Leu Glu Val Asn Gly Val Ala Leu Gln 50 55 60Gly Ala Glu His His Glu Ala Val Glu Ala Leu Arg Gly Ala Gly Thr65 70 75 80Ala Val Gln Met Arg Val Trp Arg Glu Arg Met Val Glu Pro Glu Asn 85 90 95Ala Glu Phe Ile Val Thr Asp 100341105PRTHuman papillomavirus 341Arg Glu Leu Cys Ile Gln Lys Ala Pro Gly Glu Arg Leu Gly Ile Ser1 5 10 15Ile Arg Gly Gly Ala Arg Gly His Ala Gly Asn Pro Arg Asp Pro Thr 20 25 30Asp Glu Gly Ile Phe Ile Ser Lys Val Ser Pro Thr Gly Ala Ala Gly 35 40 45Arg Asp Gly Arg Leu Arg Val Gly Leu Arg Leu Leu Glu Val Asn Gln 50 55 60Gln Ser Leu Leu Gly Leu Thr His Gly Glu Ala Val Gln Leu Leu Arg65 70 75 80Ser Val Gly Asp Thr Leu Thr Val Leu Val Cys Asp Gly Phe Glu Ala 85 90 95Ser Thr Asp Ala Ala Leu Glu Val Ser 100 105342105PRTHuman papillomavirus 342Leu Glu Gly Pro Tyr Pro Val Glu Glu Ile Arg Leu Pro Arg Ala Gly1 5 10 15Gly Pro Leu Gly Leu Ser Ile Val Gly Gly Ser Asp His Ser Ser His 20 25 30Pro Phe Gly Val Gln Glu Pro Gly Val Phe Ile Ser Lys Val Leu Pro 35 40 45Arg Gly Leu Ala Ala Arg Ser Gly Leu Arg Val Gly Asp Arg Ile Leu 50 55 60Ala Val Asn Gly Gln Asp Val Arg Asp Ala Thr His Gln Glu Ala Val65 70 75 80Ser Ala Leu Leu Arg Pro Cys Leu Glu Leu Ser Leu Leu Val Arg Arg 85 90 95Asp Pro Ala Glu Phe Ile Val Thr Asp 100 10534397PRTHuman papillomavirus 343Pro Leu Arg Gln Arg His Val Ala Cys Leu Ala Arg Ser Glu Arg Gly1 5 10 15Leu Gly Phe Ser Ile Ala Gly Gly Lys Gly Ser Thr Pro Tyr Arg Ala 20 25 30Gly Asp Ala Gly Ile Phe Val Ser Arg Ile Ala Glu Gly Gly Ala Ala 35 40 45His Arg Ala Gly Thr Leu Gln Val Gly Asp Arg Val Leu Ser Ile Asn 50 55 60Gly Val Asp Val Thr Glu Ala Arg His Asp His Ala Val Ser Leu Leu65 70 75 80Thr Ala Ala Ser Pro Thr Ile Ala Leu Leu Leu Glu Arg Glu Ala Gly85 90 95Gly344114PRTHuman papillomavirus 344Thr Leu Thr Ile Leu Arg Gln Thr Gly Gly Leu Gly Ile Ser Ile Ala1 5 10 15Gly Gly Lys Gly Ser Thr Pro Tyr Lys Gly Asp Asp Glu Gly Ile Phe 20 25 30Ile Ser Arg Val Ser Glu Glu Gly Pro Ala Ala Arg Ala Gly Val Arg 35 40 45Val Gly Asp Lys Leu Leu Glu Gly Ile Phe Val Ser Arg Ile Ala Glu 50 55 60Gly Gly Ala Ala His Arg Ala Gly Thr Leu Gln Val Gly Asp Arg Val65 70 75 80Leu Ser Ile Asn Gly Val Asp Val Thr Glu Ala Arg His Asp His Ala 85 90 95Val Ser Leu Leu Thr Ala Ala Ser Pro Thr Ile Ala Leu Leu Leu Glu 100 105 110Arg Glu34595PRTHuman papillomavirus 345Ile Pro Pro Val Thr Thr Val Leu Ile Lys Arg Pro Asp Leu Lys Tyr1 5 10 15Gln Leu Gly Phe Ser Val Gln Asn Gly Ile Ile Cys Ser Leu Met Arg 20 25 30Gly Gly Ile Ala Glu Arg Gly Gly Val Arg Val Gly His Arg Ile Ile 35 40 45Glu Ile Asn Gly Gln Ser Val Val Ala Thr Ala His Glu Lys Ile Val 50 55 60Gln Ala Leu Ser Asn Ser Val Gly Glu Ile His Met Lys Thr Met Pro65 70 75 80Ala Ala Met Phe Arg Leu Leu Thr Gly Gln Glu Asn Ser Ser Leu 85 90 95346110PRTHuman papillomavirus 346Ile His Phe Ser Asn Ser Glu Asn Cys Lys Glu Leu Gln Leu Glu Lys1 5 10 15His Lys Gly Glu Ile Leu Gly Val Val Val Val Glu Ser Gly Trp Gly 20 25 30Ser Ile Leu Pro Thr Val Ile Leu Ala Asn Met Met Asn Gly Gly Pro 35 40 45Ala Ala Arg Ser Gly Lys Leu Ser Ile Gly Asp Gln Ile Met Ser Ile 50 55 60Asn Gly Thr Ser Leu Val Gly Leu Pro Leu Ala Thr Cys Gln Gly Ile65 70 75 80Ile Lys Gly Leu Lys Asn Gln Thr Gln Val Lys Leu Asn Ile Val Ser 85 90 95Cys Pro Pro Val Thr Thr Val Leu Ile Lys Arg Asn Ser Ser 100 105 110347101PRTHuman papillomavirus 347Ile Trp Glu Gln His Thr Val Thr Leu His Arg Ala Pro Gly Phe Gly1 5 10 15Phe Gly Ile Ala Ile Ser Gly Gly Arg Asp Asn Pro His Phe Gln Ser 20 25 30Gly Glu Thr Ser Ile Val Ile Ser Asp Val Leu Lys Gly Gly Pro Ala 35 40 45Glu Gly Gln Leu Gln Glu Asn Asp Arg Val Ala Met Val Asn Gly Val 50 55 60Ser Met Asp Asn Val Glu His Ala Phe Ala Val Gln Gln Leu Arg Lys65 70 75 80Ser Gly Lys Asn Ala Lys Ile Thr Ile Arg Arg Lys Lys Lys Val Gln 85 90 95Ile Pro Asn Ser Ser 10034895PRTHuman papillomavirus 348Ile Ser Ser Gln Pro Ala Lys Pro Thr Lys Val Thr Leu Val Lys Ser1 5 10 15Arg Lys Asn Glu Glu Tyr Gly Leu Arg Leu Ala Ser His Ile Phe Val 20 25 30Lys Glu Ile Ser Gln Asp Ser Leu Ala Ala Arg Asp Gly Asn Ile Gln 35 40 45Glu Gly Asp Val Val Leu Lys Ile Asn Gly Thr Val Thr Glu Asn Met 50 55 60Ser Leu Thr Asp Ala Lys Thr Leu Ile Glu Arg Ser Lys Gly Lys Leu65 70 75 80Lys Met Val Val Gln Arg Asp Arg Ala Thr Leu Leu Asn Ser Ser 85 90 9534990PRTHuman papillomavirus 349Ile Arg Met Lys Leu Val Lys Phe Arg Lys Gly Asp Ser Val Gly Leu1 5 10 15Arg Leu Ala Gly Gly Asn Asp Val Gly Ile Phe Val Ala Gly Val Leu 20 25 30Glu Asp Ser Pro Ala Ala Lys Glu Gly Leu Glu Glu Gly Asp Gln Ile 35 40 45Leu Arg Val Asn Asn Val Asp Phe Thr Asn Ile Ile Arg Glu Glu Ala 50 55 60Val Leu Phe Leu Leu Asp Leu Pro Lys Gly Glu Glu Val Thr Ile Leu65 70 75 80Ala Gln Lys Lys Lys Asp Val Phe Ser Asn 85 9035099PRTHuman papillomavirus 350Ile Gln His Thr Val Thr Leu His Arg Ala Pro Gly Phe Gly Phe Gly1 5 10 15Ile Ala Ile Ser Gly Gly Arg Asp Asn Pro His Phe Gln Ser Gly Glu 20 25 30Thr Ser Ile Val Ile Ser Asp Val Leu Lys Gly Gly Pro Ala Glu Gly 35 40 45Gln Leu Gln Glu Asn Asp Arg Val Ala Met Val Asn Gly Val Ser Met 50 55 60Asp Asn Val Glu His Ala Phe Ala Val Gln Gln Leu Arg Lys Ser Gly65 70 75 80Lys Asn Ala Lys Ile Thr Ile Arg Arg Lys Lys Lys Val Gln Ile Pro 85 90 95Asn Ser Ser35190PRTHuman papillomavirus 351His Ala Pro Asn Thr Lys Met Val Arg Phe Lys Lys Gly Asp Ser Val1 5 10 15Gly Leu Arg Leu Ala Gly Gly Asn Asp Val Gly Ile Phe Val Ala Gly 20 25 30Ile Gln Glu Gly Thr Ser Ala Glu Gln Glu Gly Leu Gln Glu Gly Asp 35 40 45Gln Ile Leu Lys Val Asn Thr Gln Asp Phe Arg Gly Leu Val Arg Glu 50 55 60Asp Ala Val Leu Tyr Leu Leu Glu Ile Pro Lys Gly Glu Met Val Thr65 70 75 80Ile Leu Ala Gln Ser Arg Ala Asp Val Tyr 85 9035279PRTHuman papillomavirus 352Arg Val Leu Leu Met Lys Ser Arg Ala Asn Glu Glu Tyr Gly Leu Arg1 5 10 15Leu Gly Ser Gln Ile Phe Val Lys Glu Met Thr Arg Thr Gly Leu Ala 20 25 30Thr Lys Asp Gly Asn Leu His Glu Gly Asp Ile Ile Leu Lys Ile Asn 35 40 45Gly Thr Val Thr Glu Asn Met Ser Leu Thr Asp Ala Arg Lys Leu Ile 50 55 60Glu Lys Ser Arg Gly Lys Leu Gln Leu Val Val Leu Arg Asp Ser65 70 75353104PRTHuman papillomavirus 353Arg Gly Tyr Ser Pro Asp Thr Arg Val Val Arg Phe Leu Lys Gly Lys1 5 10 15Ser Ile Gly Leu Arg Leu Ala Gly Gly Asn Asp Val Gly Ile Phe Val 20 25 30Ser Gly Val Gln Ala Gly Ser Pro Ala Asp Gly Gln Gly Ile Gln Glu 35 40 45Gly Asp Gln Ile Leu Gln Val Asn Asp Val Pro Phe Gln Asn Leu Thr 50 55 60Arg Glu Glu Ala Val Gln Phe Leu Leu Gly Leu Pro Pro Gly Glu Glu65 70 75 80Met Glu Leu Val Thr Gln Arg Lys Gln Asp Ile Phe Trp Lys Met Val 85 90 95Gln Ser Glu Phe Ile Val Thr Asp 100354106PRTHuman papillomavirus 354Ile Pro Gly Asn Ser Thr Ile Trp Glu Gln His Thr Ala Thr Leu Ser1 5 10 15Lys Asp Pro Arg Arg Gly Phe Gly Ile Ala Ile Ser Gly Gly Arg Asp 20 25 30Arg Pro Gly Gly Ser Met Val Val Ser Asp Val Val Pro Gly Gly Pro 35 40 45Ala Glu Gly Arg Leu Gln Thr Gly Asp His Ile Val Met Val Asn Gly 50 55 60Val Ser Met Glu Asn Ala Thr Ser Ala Phe Ala Ile Gln Ile Leu Lys65 70 75 80Thr Cys Thr Lys Met Ala Asn Ile Thr Val Lys Arg Pro Arg Arg Ile 85 90 95His Leu Pro Ala Glu Phe Ile Val Thr Asp 100 10535598PRTHuman papillomavirus 355Gln Asp Val Gln Met Lys Pro Val Lys Ser Val Leu Val Lys Arg Arg1 5 10 15Asp Ser Glu Glu Phe Gly Val Lys Leu Gly Ser Gln Ile Phe Ile Lys 20 25 30His Ile Thr Asp Ser Gly Leu Ala Ala Arg His Arg Gly Leu Gln Glu 35 40 45Gly Asp Leu Ile Leu Gln Ile Asn Gly Val Ser Ser Gln Asn Leu Ser 50 55 60Leu Asn Asp Thr Arg Arg Leu Ile Glu Lys Ser Glu Gly Lys Leu Ser65 70 75 80Leu Leu Val Leu Arg Asp Arg Gly Gln Phe Leu Val Asn Ile Pro Asn 85 90 95Ser Ser35610PRTHuman papillomavirus 356Gln Cys Trp Arg Pro Ser Ala Thr Val Val1 5 1035710PRTHuman papillomavirus 357Trp Arg Pro Gln Arg Thr Gln Thr Gln Val1 5 1035810PRTHuman papillomavirus 358Arg Arg Arg Ile Arg Arg Glu Thr Gln Val1 5 10359148PRTHuman papillomavirus 359Met Phe Phe Pro Asn Pro Glu Glu Arg Pro Tyr Lys Leu Pro Ala Leu1 5 10 15Cys Glu Glu Val Asn Ile Ser Ile His Glu Ile Glu Leu Asp Cys Val 20 25 30Tyr Cys Glu Arg Gln Leu Tyr Arg Cys Glu Val Tyr Asp Phe Ile Phe 35 40 45Arg Asp Leu Cys Val Val Tyr Arg Lys Gly Lys Pro Leu Gly Val Cys 50 55 60Gln Pro Cys Leu Leu Phe Tyr Ser Lys Val Arg Gln Tyr Arg Arg Tyr65 70 75 80Asn Gln Ser Val Tyr Gly Arg Thr Leu Glu Asn Leu Thr Asn Lys Gln 85 90 95Leu Cys Asn Ile Leu Ile Arg Cys Gly Lys Cys Gln Lys Pro Leu Cys 100 105 110Pro Leu Glu Lys Gln Arg His Val Asp Glu Asn Lys Arg Phe His Gln 115 120 125Ile Ala Asp Gln Trp Thr Gly Arg Cys Thr Gln Cys Trp Arg Pro Ser 130 135 140Ala Thr Val Val145360149PRTHuman papillomavirus 360Met Phe Gln Asp Thr Asp Glu Lys Pro Arg Asn Leu His Glu Leu Cys1 5 10 15Glu Ala Leu Glu Thr Thr Val His Glu Ile Ser Leu Pro Cys Val Gln 20 25 30Cys Lys Lys Thr Leu Asp Arg Asn Glu Val Tyr Asp Phe Leu Phe Thr 35 40 45Asp Leu Lys Ile Val Tyr Arg Cys Gly Asn Pro Tyr Gly Val Cys Lys 50 55 60Gln Cys Leu Arg Leu Leu Ser Lys Val Ser Glu Tyr Arg Tyr Phe Asn65 70 75 80Tyr Ser Val Tyr Gly Asn Thr Leu Glu Glu Ile Val His Lys Pro Leu 85 90 95Asn Glu Ile Thr Ile Arg Cys Ile Thr Cys Gln

Arg Pro Leu Cys Pro 100 105 110Gln Glu Lys Gln Arg His Val Asp Arg Lys Lys Arg Phe His Asn Ile 115 120 125Ser Asn Arg Trp Thr Gly Arg Cys Ser Val Cys Trp Arg Pro Gln Arg 130 135 140Thr Gln Thr Gln Val145361158PRTHuman papillomavirus 361Met Ala Arg Phe Pro Asn Pro Ala Glu Arg Pro Tyr Lys Leu Pro Asp1 5 10 15Leu Cys Thr Ala Leu Asp Thr Thr Leu His Asp Ile Thr Ile Asp Cys 20 25 30Val Tyr Cys Lys Thr Gln Leu Gln Gln Thr Glu Val Tyr Glu Phe Ala 35 40 45Phe Ser Asp Leu Phe Ile Val Tyr Arg Asn Gly Glu Pro Tyr Ala Ala 50 55 60Cys Gln Lys Cys Ile Lys Phe His Ala Lys Val Arg Glu Leu Arg His65 70 75 80Tyr Ser Asn Ser Val Tyr Ala Thr Thr Leu Glu Ser Ile Thr Asn Thr 85 90 95Lys Leu Tyr Asn Leu Ser Ile Arg Cys Met Ser Cys Leu Lys Pro Leu 100 105 110Cys Pro Ala Glu Lys Leu Arg His Val Asn Thr Lys Arg Arg Phe His 115 120 125Gln Ile Ala Gly Ser Tyr Thr Gly Gln Cys Arg His Cys Trp Thr Ser 130 135 140Asn Arg Glu Asp Arg Arg Arg Ile Arg Arg Glu Thr Gln Val145 150 1553624PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 362Gly Leu Gly Phe13638PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 363Xaa Xaa Arg Phe His Xaa Ile Xaa1 53648PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 364Leu Xaa Ile Arg Cys Xaa Xaa Cys1 53658PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 365Xaa Cys Xaa Xaa Pro Leu Xaa Pro1 53668PRTArtificial SequenceDescription of Artificial Sequence Synthetic peptide 366Xaa Pro Leu Xaa Pro Xaa Glu Lys1 5

Claims

1. An antibody composition comprising a mixture of monoclonal antibodies that specifically bind to E6 proteins of HPV strains 16, 18, 31, 33 and 45, wherein at least one of said monoclonal antibodies specifically binds to E6 proteins of at least three different oncogenic HPV strains.

2. The antibody composition claim 1, wherein said mixture of monoclonal antibodies specifically bind to E6 proteins of HPV strains 16, 18, 31, 33, 45, 52 and 58.

3. The antibody composition claim 1, wherein said mixture of monoclonal antibodies specifically bind to E6 proteins of HPV strains 16, 18, 31, 33, 45, 52, 58, 35 and 59.

4. The antibody composition of claim 1, wherein at least two of said monoclonal antibodies specifically bind to E6 proteins of at least six different oncogenic HPV strains.

5. A diagnostic kit for the detection of an HPV E6 polypeptide in a sample, comprising:the antibody composition of claim 1.

6. The diagnostic kit of claim 5, wherein said monoclonal antibodies are labeled.

7. The diagnostic kit of claim 5, further comprising instructions for using said antibody composition to detect an oncogenic HPV E6 polypeptide in a sample.

8. The diagnostic kit of claim 5, further comprising a PDZ domain polypeptide that binds to an oncogenic HPV E6 polypeptide in a sample.

9. A method of detecting an HPV E6 protein in a sample, comprising:contacting an antibody composition of claim 1 with said sample; anddetecting any binding of said antibody to said sample;wherein binding of said antibody to said sample indicates the presence of an HPV E6 protein.

10. The method of claim 9, wherein said sample is suspected of containing an oncogenic strain of HPV.

11. A method of detecting the presence of an oncogenic HPV E6 protein in a sample, said method comprising:contacting a sample with a PDZ domain polypeptide; and,detecting any binding of said oncogenic HPV E6 protein in said sample to said PDZ domain polypeptide using an antibody composition of claim 1;wherein binding of said oncogenic HPV E6 protein to said PDZ domain polypeptide indicates the presence of an oncogenic HPV E6 protein in said sample.

12. A system for detecting the presence of an oncogenic HPV E6 polypeptide in a sample, said method comprising:a first and a second binding partner for an oncogenic HPV E6 polypeptide,wherein said first binding partner is a PDZ domain protein and said second binding partner is an antibody that specifically binds to the E6 proteins of at least three different oncogenic HPV strains.

13. The system of claim 12, wherein at least one of said binding partners is attached to a solid support.

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