title: Human T helper cell epitopes overlap B cell and putative cytotoxic T cell epitopes in the E2 protein of human papillomavirus type 16.
abstract: Activation of T helper cells is a prerequisite for the function of cytotoxic T lymphocytes (CTL) and the maturation of the B cell response. Because epitopes recognized by each of these cells may overlap, we scanned the E2 protein of human papillomavirus (HPV) type 16 to identify the T helper cell epitopes. Four major T helper cell epitopes (mapping between aa:s 11-25, 141-155, 191-205 & 231-245) and adjacent human B cell epitopes were found. The first peptide-defined epitope (RLNV) 11CQDKILTHYENDSTD25 overlapped five putative HLA-I (A1, A2, A0205, A3 & A11) binding motifs (CQDKILTHY, RLNVCQDKI, NVCQDKIL, RLNVCQDK & RLNVCQDK). This epitope is also part of an N-terminal alpha-helix which may form four HLA-II (DR2, DR4, DR7 & DR8) specific agretopes for structures recognizable by the T cell receptor (e.g. KILT). The second epitope 141EEASVTVVEGOVDYY155 (GLYY) overlapped the putative HLA-A1 & HLA-Bw37 binding motifs (VVEGQVDYY/QVDYYGLYY and EEASVTVV), and two HLA-II (DR1 & DR3) specific agretopes. The third and fourth epitopes were not associated with more than one putative CTL epitope each. Only the first epitope shared considerable aa-homology with corresponding regions of other genital HPV types.
authors.affiliation: Dept of Chronic Viral Diseases, National Public Health Inst, Helsinki, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Lehtinen
authors.forename: M H
authors.initials: MH
authors.lastname: Hibma
authors.forename: G
authors.initials: G
authors.lastname: Stellato
authors.forename: T
authors.initials: T
authors.lastname: Kuoppala
authors.forename: J
authors.initials: J
authors.lastname: Paavonen
mesh_terms: D000595:Amino Acid Sequence; D002277:Carcinoma / Q000276:immunology; D004268:DNA-Binding Proteins; D018604:Epitope Mapping; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology; D002578:Uterine Cervical Dysplasia / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D009856:Oncogene Proteins, Viral; D014764:Viral Proteins