Cervical carcinoma cells transfected with the CD80 gene elicit a primary cytotoxic T lymphocyte response specific for HPV 16 E7 antigens.
Cervical carcinoma is strongly associated with human papillomavirus (HPV) type 16, and the transforming viral genes E6 and F7 are steadily expressed by the tumor cells. Therefore these viral oncogenes may be regarded as tumor-associated antigens. Our previous studies showed that cervical cancer cells after introduction of the CD80 gene activated allogeneic cytotoxic T lymphocytes (CTLs). In this study, we tested whether HPV 16+ cervical tumor cells (CaSki) expressing CD80 were able to activate CTLs recognizing HPV 16 E7 antigen. To this end, CD80+ CaSki cells (HLA-A*0201+) were used to stimulate peripheral blood T lymphocytes from HLA-A*0201+ healthy donors. We found that the activated T cells were able to lyse parental CaSki cells as well as Epstein-Barr virus-immortalized autologous B cells loaded with HLA-A*0201-restricted E7 peptides (amino acids 11-19, 82-90, 86-93). In contrast, no lysis was observed against target cells loaded with a control HIV-reverse transcriptase peptide (amino acid 476-484, HLA-A 0201-restricted). Our data, for the first time, provide evidence that CD80-expressing cervical cancer cells are able to activate tumor-specific CTLs using HPV 16 E7 as tumor-associated antigens.
Kaufmann
A M
AM
Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Gissmann
L
L
Schreckenberger
C
C
Qiao
L
L
D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D015234:HLA-A Antigens / Q000276:immunology; D004854:Herpesvirus 4, Human; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis* / Q000276:immunology; D027383:Papillomaviridae / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000528:radiation effects; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000276:immunology*
D018122:B7-1 Antigen; D015234:HLA-A Antigens; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011994:Recombinant Proteins; C059731:oncogene protein E7, Human papillomavirus type 16