title: Human papillomavirus type 33 E7 peptides presented by HLA-DR*0402 to tumor-infiltrating T cells in cervical cancer.
abstract: Several characteristics make human papillomavirus (HPV) amenable to vaccination. Anti-HPV-directed vaccines are based on the observation that HPV E6 and E7 oncoproteins are constitutively expressed in HPV-positive cervical cancer and may serve as tumor rejection antigens. Five HPV types (16, 18, 31, 33, and 45) account for 80% of cervical cancer. Until now, the type of immune response capable of mediating an effective antitumor response has not been defined. In order to define the anticancer-directed immune response in situ, we characterized CD4(+) and CD8(+) sorted T cells from peripheral blood lymphocytes, freshly harvested tumor tissue, and tumor-infiltrating lymphocytes (TIL) from a patient with cervical cancer. The HLA-DR-restricted CD4(+) T-cell receptor VB16-, VA10-, VA21-, and VA22-positive CD4(+) T-cell line derived from TIL recognizes autologous HLA-DR*0402(+) (HPV33(+)) cervical cancer cells, as determined by gamma interferon secretion. Testing of different peptides spanning the E7 gene revealed that the HPV33(73-87) peptide ASDLRTIQQLLMGTV represents the immunodominant epitope which can also be presented by the DR*0401 allele to TIL. Such major histocompatibility complex class II-presented peptides represent attractive candidates to augment T-cell responses directed against autologous tumor cells.
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: K
authors.initials: K
authors.lastname: Freitag
authors.forename: A
authors.initials: A
authors.lastname: Necker
authors.forename: M J
authors.initials: MJ
authors.lastname: Maeurer
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D000939:Epitopes; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000737:chemistry / Q000276:immunology*; D027383:Papillomaviridae / Q000737:chemistry / Q000276:immunology*; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000473:pathology / Q000821:virology*
chemical_list: C410917:E7 protein, Human papillomavirus type 33; D000939:Epitopes; D006684:HLA-DR Antigens; D009856:Oncogene Proteins, Viral; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma