A therapy-related point mutation changes the HLA restriction of an HIV-1 Pol epitope from A2 to B57 and enhances its recognition.
In this study, we investigated CD8 T-cell recognition of wild-type HIV-1 Pol (RT 210-220) peptide LRWGFTTPDKK and of several variants incorporating common antiretroviral therapy-associated mutations (L210W, T215Y, Y215C). LRWGFTTPDKK was weakly and infrequently recognized in the context of HLA-A2. However, the 215C mutation created a strong, commonly recognized HLA-B57-restricted epitope. An antiretroviral therapy-associated mutation thus alters the HLA restriction of a weak Pol epitope, potentially enhancing CD8 T-cell recognition of HIV.
Mason
Rosemarie D
RD
Immunology Program, Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada A1B 3V6.
Grant
Michael D
MD
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D024882:Drug Resistance, Viral / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology; D015684:Gene Products, pol / Q000235:genetics* / Q000276:immunology; D054303:HIV Reverse Transcriptase / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D006801:Humans; D017354:Point Mutation
D018984:Epitopes, T-Lymphocyte; D015684:Gene Products, pol; D015789:HLA-A2 Antigen; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D054303:HIV Reverse Transcriptase