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) cel l lines, T cells from a human papillomavirus (HPV) type 16-positive pa tient with a cervical carcinoma in situ and from a healthy volunteer w ere stimulated in vitro with autologous dendritic cells loaded with pe ptides derived from the viral transforming proteins E6 and E7 and corr esponding to potential HLA-A0201-restricted T cell epitopes. From eac h donor a small number of low-affinity CTL lines against the peptide E 7/86-93 was obtained, which specifically lysed HLA-A0201-expressing B -lymphocytes (cell line 721) loaded with this peptide. Cytotoxicity wa s also observed against two HLA-A0201-E7-positive epithelial cell lin es, the cervical carcinoma cell line CaSki and the HPV-16-immortalized foreskin-keratinocyte cell line HPK IA. However, since none of the CT L recognized both cell lines, and E7-expressing 721 transfectants were never lysed, it was concluded that the reactivity against CaSki and H PK IA cells was due to cross-reactivity on allogeneic HLA molecules ra ther than to E7 recognition, which emphasizes that the specificity of tumour cell lysis by peptide-induced CTL has to be interpreted with ca ution.