HUMAN CYTOTOXIC T-LYMPHOCYTES STIMULATED BY ENDOGENOUSLY PROCESSED HUMAN PAPILLOMAVIRUS TYPE-11 E7 RECOGNIZE A PEPTIDE-CONTAINING A HLA-A2 (A-ASTERISK-0201) MOTIF

Cytotoxic T lymphocytes (CTL) may play an important role in the contro l of human papillomavirus (HPV)-induced anogenital neoplasias, but hav e been difficult to study owing to the difficulty in obtaining suffici ent quantities of infectious virus. To address this we have stimulated human HPV-specific CTL in vivo using low-density cells (LDC) from per ipheral blood mononuclear cells (PBMC). Low-density cells were used to present synthetic peptides, or endogenously processed peptides expres sed from recombinant vaccinia viruses, to high-density PBMC (predomina ntly lymphocytes) for 6 days. Cytotoxic T lymphocytes stimulated with endogenously processed HPV 11 E7 recognized the synthetic HLA-A2 (A02 01) motif-containing nonamer, 4-12. In reciprocal experiments, CTL sti mulated with this peptide in vitro recognized targets expressing endog enously processed E7. The responses in each case were A2 restricted an d peptide specific. Two additional A2 motif-containing nonamers from H PV 6b E7 (21-30 and 47-55) also elicited peptide-specific, A2-restrict ed CTL. The data illustrate the potential that in vitro stimulation wi th LDC has in understanding CTL responses to experimentally problemati c viral systems such as HPV, and may offer a route to specific immunot herapy of HPV-associated lesions.