Conserved CTL epitopes shared between HIV-infected human long-term survivors and chimpanzees

Certain HIV-1 infected humans that do not progress to AIDS have been docume nted to share particular MHC class I alleles that appear to correlate with long-term survival. HIV-1-infected chimpanzees are relatively resistant to progression to AIDS. Out of a group of 10 chimpanzees with CTE activity and nonprogressive HIV-1 infection, 2 animals with prominent cytolytic CD3(+)C D8(+) T cell responses to HIV-1 Ags were studied in detail. Characterizatio n of these CTL revealed that they contained the granzymes A and B, T cell i ntracellular Ag-1, and perforin and induced calcium-dependent cytolysis tha t correlated with the presence of apoptotic nuclei in target cells. These C TL responses were directed against two gag peptides, which were found to be identical to previously described epitopes recognized in the context of HL A-B27 and HLA-B57 molecules. The latter two restriction elements occur with increased frequency in human long-term survivor cohorts. Phylogenetic comp arisons revealed that the chimpanzee restriction elements, Patr-B*02 and -B *03, described here do not show any obvious similarity with the HLA-B*27 an d -B*57 alleles, suggesting that CTL responses to HIV-1 in distinct primate species may be controlled by different types of HLA-B-like molecules. The CTL responses in these two chimpanzees are directed, however, against highl y conserved epitopes mapping across the majority of HIV-1 clades.