Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1) exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences and HLA-II allelic data, we identified 29 HLA-II associated HIV sequence polymorphisms or adaptations (HLA-AP) in an African cohort of chronically HIV-infected individuals. Epitopes encompassing the predicted adaptation (AE) or its non-adapted (NAE) version were evaluated for immunogenicity. Using a CD8-depleted IFN-? ELISpot assay, we determined that the magnitude of CD4+ T cell responses to the predicted epitopes in controllers was higher compared to non-controllers (p<0.0001). however, regardless of the group, magnitude responses to ae was lower as compared nae (p<0.0001). cd4+ t cell in patients with acute hiv infection (ahi) demonstrated poor immunogenicity towards encoded by their transmitted founder virus. longitudinal data ahi off antiretroviral therapy sequence changes that were biologically confirmed represent escape mutations. these demonstrate an innovative application hla-associated polymorphisms identify relevant epitopes and suggests cells are active participants driving evolution.
Journal: PLoS pathogens
DOI: 10.1371/journal.ppat.1005111
Year: 2015