Impact of APOBEC Mutations on CD8+ T Cell Recognition of HIV Epitopes Varies Depending on the Restricting HLA.

We previously showed that APOBEC-mediated mutations in HIV CD8 T-cell epitopes generally reduce recognition by CD8 T cells. Here, we examined this effect in the context of histocompatibility-linked leukocyte antigen (HLA) alleles differentially associated with disease progression rates. For HLA-B57-restricted epitopes, APOBEC mutations generally diminished CD8 T cell recognition. Conversely, recognition of HLA-B35-restricted epitopes was consistently enhanced. For epitopes that can be presented by either HLA-A2 or A3, the same APOBEC mutation had differential effects on CD8 T cell recognition, depending on the individual's HLA genotype. The pattern of HLA dependence provides additional evidence that APOBEC action is channeled toward cytotoxic CD8 T-cell escape.