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The extreme polymorphism in the human leukocyte antigen (HLA) class I region of the human genome is suggested to provide an advantage in pathogen defence mediated by CD8⁺ T cells^,,. HLA class I molecules present pathogen-derived peptides on the surface of infected cells for recognition by CD8⁺ T cells. However, the relative contributions of HLA-A and -B alleles have not been evaluated. We performed a comprehensive analysis of the class I restricted CD8⁺ T-cell responses against human immunodeficiency virus (HIV-1), immune control of which is dependent upon virus-specific CD8⁺ T-cell activity^,. In 375 HIV-1-infected study subjects from southern Africa, a significantly greater number of CD8⁺ T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P = 0.0033). Here we show that variation in viral set-point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort …