NATURALLY PROCESSED VIRAL PEPTIDES RECOGNIZED BY CYTOTOXIC T-LYMPHOCYTES ON CELLS CHRONICALLY INFECTED BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

We have established long-term cultures of several cell lines stably an d uniformly expressing human immunodeficiency virus type 1 (HIV-1) in order to (a) identify naturally processed HIV-1 peptides recognized by cytotoxic T lymphocytes (CTL) from HIV-1-seropositive individuals and (b) consider the hypothesis that naturally occurring epitope densitie s on HIV-infected cells may limit their lysis by CTL. Each of two A2-r estricted CD8(+) CTL specific for HIV-1 gag or reverse transcriptase ( RT) recognized a single naturally processed HIV-1 peptide in trifluoro acetic acid (TEA) extracts of infected cells: gag 77-85 (SLYNTVATL) or RT 476-484 (ILKEPVHGV). Both processed peptides match the synthetic p eptides that are optimally active in cytotoxicity assays and have the consensus motif described for A2-associated peptides. Their abundances were approximate to 400 and approximate to 12 molecules per infected Jurkat-A2 cell, respectively. Other synthetic HIV-1 peptides active at subnanomolar concentrations were not present in infected cells. Excep t for the antigen processing mutant line T2, HIV-infected HLA-A2(+) ce ll lines were specifically lysed by both A2-restricted CTL, although i nfected Jurkat-A2 cells were lysed more poorly by RT-specific CTL than by gag-specific CTL, suggesting that low cell surface density of a na tural peptide may limit the effectiveness of some HIV-specific CTL des pite their vigorous activity against synthetic peptide-treated target cells.