Human leucocyte antigen supertypes and immune susceptibility to HIV-1, implications for vaccine design

T cell responses against HIV-1 have been identified in a number of exposed uninfected populations. We hypothesized that the ability to mount an effect ive T cell response is partly determined by the human leucocyte antigens (H LA) phenotype of the individual. We examined whether certain HLA supertypes were associated with differential HIV-1 susceptibility in sexually exposed adults and in the setting of mother to child HIV-1 transmission. By multiv ariate analysis, decreased HIV-1 infection risk was strongly associated wit h possession of a cluster of closely related class I HLA alleles (A2/6802 s upertype) in sexually exposed adults (Hazard ratio = 0.42, 95% confidence i ntervals (CI): 0.22-0.81, P = 0.009) and perinatally exposed infants (Odds ratio = 0.12, 95% CI: 0.03-0.54, P = 0.006). The alleles in this HLA supert ype are known in some cases, to present the same peptide epitopes (termed ' supertopes'), for T cell recognition. The identification of HIV-1 supertope s, which are associated with protection from HIV-1 infection, has important implications for the application of epitope-based HIV-1 vaccines in a vari ety of racial groups. (C) 2001 Elsevier Science B.V. All rights reserved.