HLA-A2-restricted peripheral blood cytolytic T lymphocyte response to HPV type 16 proteins E6 and E7 from patients with neoplastic cervical lesions.
The DNA from human papillomavirus (HPV) can be detected in 90% of cervical carcinomas. To address whether patients infected with HPV can mount efficient T cell responses to this pathogen we examined the cytotoxic T lymphocyte (CTL) response of peripheral blood mononuclear cells (PBMC) from patients with abnormal genital epithelial cells. PBMC from 11 HLA-A2+ patients were stimulated with CaSki, a cervical carcinoma cell line that is HPV 16+ and HLA-A2+. The CTL were screened for reactivity to the cervical carcinoma cell line C33A (HPV-, HLA-A2+) transfected with the HPV 16 E6 or E7 genes or the plasmid without insert. The CTL of 1 patient showed particularly strong CaSki and HPV E6 or E7 protein-specific cytotoxicity in a HLA-A2+-restricted fashion. In contrast, these CTL lysed neither a vector-only transfectant, the natural killer cell (NK) target, K562 nor the lymphokine-activated killer cell (LAK) target, Daudi. HLA-A2 restriction was demonstrated by the lack of recognition of a HLA-A2- CaSki cell line developed in our laboratory. The CTL line was cloned and 99 clones were harvested and screened; 51 clones lysed CaSki, of which 17 did not lyse the A2- CaSki. Of these HLA-A2- restricted clones, 8 did not lyse C33A transfectants, 6 lysed all C33A transfectants, 3 lysed C33A-E7 only and none lysed C33A-E6 only. These data imply that, within the bulk CTL line, HLA-A2-restricted recognition of antigens was restricted to CaSki antigens, antigens common to cervical carcinoma (CaSki plus C33A), or HPV-16-E7-derived antigen on the clonal level. The E7-restricted clones were negative for recognition of known HLA-A2-binding peptides from E7.
Evans
C
C
Institute for Medical Microbiology, Technical University of Munich, Germany.
Bauer
S
S
Grubert
T
T
Brucker
C
C
Baur
S
S
Heeg
K
K
Wagner
H
H
Lipford
G B
GB
D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000276:immunology* / Q000378:metabolism; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; D012680:Sensitivity and Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000097:blood / Q000276:immunology* / Q000821:virology*
C068651:E6 protein, Human papillomavirus type 16; D015789:HLA-A2 Antigen; D015395:Histocompatibility Antigens Class I; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16