Epitope Cross-Reactivity Frequently Differs between Central and Effector Memory HIV-Specific CD8+ T Cells

Abstract

HIV diversity may limit the breadth of vaccine coverage due to epitope sequence differences between strains. Although amino acid substitutions within CD8+ T cell HIV epitopes can result in complete or partial abrogation of responses, this has primarily been demonstrated in effector CD8+ T cells. In an HIV-infected Kenyan cohort, we demonstrate that the cross-reactivity of HIV epitope variants differs dramatically between overnight IFN-γ and longer-term proliferation assays. For most epitopes, particular variants (not the index peptide) were preferred in proliferation in the absence of corresponding overnight IFN-γ responses and in the absence of the variant in the HIV quasispecies. Most proliferating CD8+ T cells were polyfunctional via cytokine analyses. A trend to positive correlation was observed between proliferation (but not IFN-γ) and CD4 counts. We present findings relevant to the assessment of HIV vaccine candidates and toward a better understanding of how viral diversity is tolerated by central and effector memory CD8+ T cells.