IDENTIFICATION OF TYPE-SPECIFIC CYTOTOXIC T-LYMPHOCYTE RESPONSES TO HOMOLOGOUS VIRAL-PROTEINS IN LABORATORY WORKERS ACCIDENTALLY INFECTED WITH HIV-1

Characterization of the cytotoxic T lymphocyte (CTL) response against HIV-I has been limited by the use of target cells expressing viral pro teins from laboratory isolates of HIV-1. This approach has favored ide ntification of group-specific CTL responses and precluded assessment o f the extent of type-specific CTL responses directed against HIV-1. Us ing cells expressing viral proteins from the HIV-1 IIIB strain, we per formed a detailed characterization of HIV-1-specific CTL response in t hree laboratory workers accidentally infected with HIV-1 IIIB. Eight o f the epitopes identified were group specific, lying in relatively con served regions of Gag, reverse transcriptase, and envelope. Three type -specific epitopes were identified, two of them in highly variable reg ions of envelope. In longitudinal studies in one subject, seven differ ent epitopes and five different restricting HLA class I alleles were i dentified, with a progressive increase in the number of CTL epitopes r ecognized by this subject over time. Our data demonstrate that type-sp ecific CTL responses make up a significant proportion of the host cell ular immune response against HIV-I and that a broadening of epitope sp ecificity may occur.