An HLA-directed molecular and bioinformatics approach identifies new HLA-A11 HIV-1 subtype E cytotoxic T lymphocyte epitopes in HIV-1-infected thais

Only limited cytotoxic T lymphocyte (CTL) epitope mapping has been done in nonsubtype B HIV-infected persons. We used molecular immunogenetic tools to determine HIV-specific CTL responses in HIV-1 Env subtype E-infected femal e sex workers (FSWs) from northern Thailand, where more than 50% of the pop ulation is HLA-A11 positive. EpiMatrix, a computer-based T cell epitope pre diction algorithm, and a manual editing approach were used to predict 77 po ssible HLA-A11 CTL epitopes in HIV-1, some of which were conserved between subtypes B and E, MHC binding of these peptides was determined in an HLA-A1 1 stabilization assay, and binding peptides were tested for CTL recognition in eight HLA-A11-positive FSWs, Subtype E versions of known HLA-A2 subtype B HIV epitopes were also tested in four HLA-A2 positive FSWs, CTL response s were detected in all HLA-A11-positive and in three of four HLA-A2-positiv e persons. Among the 12 FSWs responses to peptides were found to Pol in 9 ( 75%), Env in 7 (58%), Nef in 5 (42%), and Gag in 5 (42%), and to conserved epitopes in 8 (67%), To identify HLA-A11 CTL epitopes in the absence of pre diction tools, it would have been necessary to test almost 3000 10-mer pept ides, EpiMatrix and manual predictions reduced this number to 77, of which 26 were MHC binding and 12 were CTL epitopes, Six of these HLA-A11 CTL epit opes have not been previously reported and are located in RT, gp120, and gp 41. This report of CTL responses in subtype E-infected individuals defines epitopes that may be useful in HIV pathogenesis or vaccine studies.