CHARACTERIZATION OF HLA-B57-RESTRICTED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 GAG-SPECIFIC AND RT-SPECIFIC CYTOTOXIC T-LYMPHOCYTE RESPONSES

HLA-B57 has been shown to be strongly associated with slow disease pro gression in human immunodeficiency virus type 1 (HIV-1)-infected patie nts from the Amsterdam Cohort. Since HIV-1-specific CTL can control an d eliminate virus-infected cells, we sought to characterize the domina nt HLA-B57-restricted CTL responses at the epitope level, It was found that HLA-B57-restricted CTL responses were targeted at multiple prote ins of HIV-1, with CTL specific for Gag and RT being the most pronounc ed, Gag-specific CTL recognized peptides ISPRTLNAW (aa 147-155) and ST LQEQIGW (aa 241-249), which had previously been reported as HLA-B57-re stricted,The RT-specific CTL response in one longterm survivor studied in great detail persisted for > 10 years and was dominated by HLA-B57 -restricted CTL that recognized the newly defined epitope IVLPEKDSW (R TLAI, aa 244-252), This epitope could be recognized in the context of both HLA-B5701 and HLA-B*5801. Interestingly, three epitope variants of IVLPEKDSW were observed, which coincided with the strongest detecta ble CTL response to RT, One variant (T2E7) was not recognized by IVLPE KDSW-specific CTL despite the fact that this variant bound to HLA-B57 01 with a similar affinity as the index peptide. Finally, only viruses which contained the epitope index sequence were obtained suggesting e fficient virus control by CTL, In conclusion, we report the characteri zation of dominant HIV-1 Gag- and RT-derived, HLA-B57-restricted CTL e pitopes which are associated with longer time to AIDS. Further charact erization of CTL responses restricted by HLA-B57 and other protective HLA alleles may contribute to the development of effective AIDS vaccin es.