title: CD4+ tumor-infiltrating lymphocytes in cervical cancer recognize HLA-DR-restricted peptides provided by human papillomavirus-E7.
abstract: Human papillomavirus (HPV)-encoded proteins may provide targets for CD8+ or CD4+ T lymphocytes infiltrating into cervical cancer. We established an MHC class II-restricted CD4+ T cell line from a patient with cervical cancer that recognizes autologous (HPV35+, HPV59+) cervical cancer cells and the HLA-DR4-matched cervical cancer cell line Me180 (HPV68+) as determined by TNF-alpha secretion. Expression of different HPV-E7 genes in autologous B cells revealed that this T cell line defines a DR4-presented T cell epitope that is shared among the E7 genes of HPV59 and HPV68. MHC class II-presented peptides may be implemented to augment T cell responses directed against autologous tumor cells, particularly if cancer cells lack MHC class I expression, which is a frequent event in the evolution of cervical cancer.
authors.affiliation: Department of Medical Microbiology, Johannes Gutenberg University, Mainz, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Höhn
authors.forename: H
authors.initials: H
authors.lastname: Pilch
authors.forename: S
authors.initials: S
authors.lastname: Günzel
authors.forename: C
authors.initials: C
authors.lastname: Neukirch
authors.forename: C
authors.initials: C
authors.lastname: Hilmes
authors.forename: A
authors.initials: A
authors.lastname: Kaufmann
authors.forename: B
authors.initials: B
authors.lastname: Seliger
authors.forename: M J
authors.initials: MJ
authors.lastname: Maeurer
mesh_terms: D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009856:Oncogene Proteins, Viral / Q000276:immunology / Q000378:metabolism; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010455:Peptides; C059731:oncogene protein E7, Human papillomavirus type 16