HLA-A2-RESTRICTED PERIPHERAL-BLOOD CYTOLYTIC T-LYMPHOCYTE RESPONSE TOHPV TYPE-16 PROTEINS E6 AND E7 FROM PATIENTS WITH NEOPLASTIC CERVICALLESIONS

The DNA from human papillomavirus (HPV) can be detected in 90% of cerv ical carcinomas. To address whether patients infected with HPV can mou nt efficient T cell responses to this pathogen we examined the cytotox ic 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 inse rt. The CTL of 1 patient showed particularly strong CaSki and HPV E6 o r E7 protein-specific cytotoxicity in a HLA-A2-restricted fashion. In contrast, these CTL lysed neither a vector-only transfectant, the natu ral killer cell (NK) target, K562 nor the lymphokine-activated killer cell (LAK) target, Daudi. HLA-A2 restriction was demonstrated by the l ack of recognition of a HLA-A2(-) CaSki cell line developed in our lab oratory. The CTL line was cloned and 99 clones were harvested and scre ened; 51 clones lysed CaSki, of which 17 did not lyse the A2(-) CaSki. Of these HLA-A2(-) restricted clones, 8 did not lyse C33A transfectan ts, 6 lysed all C33A transfectants, 3 lysed C33A-E7 only and none lyse d C33A-E6 only. These data imply that, within the bulk CTL line, HLA-A 2-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 ne gative for recognition of known HLA-A2-binding peptides from E7.