IDENTIFICATION AND CHARACTERIZATION OF MULTIPLE HLA-A24-RESTRICTED HIV-1 CTL EPITOPES - STRONG EPITOPES ARE DERIVED FROM V-REGION OF HIV-1

HIV-I-specific CTL has a crucial role in the elimination of the virus. However, a restricted number of common HLA class I alleles has been s tudied for their presentation of HIV-1 CTL epitopes. We have attempted to identify HIV-1 CTL epitopes presented by HLA-A2402 using reverse immunogenetics. Fifty-three HLA-A2402-binding HIV-1 peptides were use d to induce specific CTL in PBL of four HIV-l-infected individuals car rying HLA-A24. Twelve peptides were strongly suggested to be HLA-A240 2-restricted HIV-1 CTL epitopes because these peptides induced the spe cific CTL that killed both the target cells pulsed with the specific p eptides and those infected with the vaccinia HIV-1 recombinant virus i n at least one HIV-l-infected individual. Of these epitopes, 11 were c onfirmed by the generation of the specific CTL clones. Six were the En v epitopes while three, one, and one were derived from Gag, Pol, and N ef proteins, respectively. Analysis of 12 HIV-l-infected individuals u sing these peptides showed that 5 derived from the Env protein and one from the Nef protein were strong epitopes. These strong epitopes were derived from the diverse region of HIV-1 while weak epitopes were con served in the HIV-1 clade B strain. Analysis of CTL recognition of mut ations in these strong epitopes suggested that the mutations in the En v epitopes may critically influence CTL recognition in vivo.