EVIDENCE OF PRESENTATION OF MULTIPLE HIV-1 CYTOTOXIC T-LYMPHOCYTE EPITOPES BY HLA-B-ASTERISK-3501 MOLECULES THAT ARE ASSOCIATED WITH THE ACCELERATED PROGRESSION OF AIDS

We recently showed HLA-B35-restricted CTL activity for 10 HIV-1 epitop es in PBL from two HIV-l-infected individuals. In the present study, w e established CTL clones specific for nine of these HIV-1 epitopes to confirm these HLA-B35-restricted epitopes, The specific CTL clones eff ectively killed the HLA-B3501-positive target cells infected with the HIV-1 vaccinia recombinant virus. These results confirmed that nine H IV-1 CTL epitopes are presented by HLA-B3501 molecules. The CTL activ ity specific for four Pol and two Nef epitopes was induced in the pept ide-stimulated PBL from three or more of seven HIV-1-infected individu als, indicating that these six are common epitopes. Eight were conside red strong epitopes because the specific CTL activity was detected in the cultured PBL that was once stimulated with peptides. Thus, the pre sent study excluded the possibility that the disability of the present ation of HIV-1 epitopes by HLA-B35 molecules is associated with the ac celerated progression of AIDS in HLA-B35-positive individuals. Analysi s of mutated epitopes found in an HIV-1 type B strain using the CTL cl ones revealed that most mutated epitopes partially or markedly affect the recognition of CTL clones. Of 19 mutations that affected recogniti on of the CTL clones, 7 reduced peptide-HLA-B3501 binding, while 12 a ffected TCR recognition. These results indicate that natural mutations of HLA-BS5-restricted HIV-1 CTL epitopes affect the recognition of CT L by mechanisms that reduce both peptide binding and TCR recognition.