Specificity of human cytotoxic T lymphocytes induced by a human papillomavirus type 16 E7-derived peptide.
In order to establish tumour-specific cytotoxic T lymphocyte (CTL) cell lines, T cells from a human papillomavirus (HPV) type 16-positive patient with a cervical carcinoma in situ and from a healthy volunteer were stimulated in vitro with autologous dendritic cells loaded with peptides derived from the viral transforming proteins E6 and E7 and corresponding to potential HLA-A*0201-restricted T cell epitopes. From each donor a small number of low-affinity CTL lines against the peptide E7/86-93 was obtained, which specifically lysed HLA-A*0201-expressing B-lymphocytes (cell line 721) loaded with this peptide. Cytotoxicity was also observed against two HLA-A*0201-E7-positive epithelial cell lines, the cervical carcinoma cell line CaSki and the HPV-16-immortalized foreskin-keratinocyte cell line HPK IA. However, since none of the CTL recognized both cell lines, and E7-expressing 721 transfectants were never lysed, it was concluded that the reactivity against CaSki and HPK IA cells was due to cross-reactivity on allogeneic HLA molecules rather than to E7 recognition, which emphasizes that the specificity of tumour cell lysis by peptide-induced CTL has to be interpreted with caution.
Jochmus
I
I
Deutsches Krebsforschungszentrum, Heidelberg, Germany. jochmus@dkfz-heidelberg.de
Osen
W
W
Altmann
A
A
Buck
G
G
Hofmann
B
B
Schneider
A
A
Gissmann
L
L
Rammensee
H G
HG
D002278:Carcinoma in Situ / Q000276:immunology*; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D027383:Papillomaviridae / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology* / Q000821:virology; D010455:Peptides / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000276:immunology* / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000276:immunology*
D015789:HLA-A2 Antigen; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D010455:Peptides; C059731:oncogene protein E7, Human papillomavirus type 16