Differential immunodominance hierarchy of CD8+ T-cell responses in HLA-B*27:05- and -B*27:02-mediated control of HIV-1 infection. Journal of Virology
The association between HLA-B*27:05 and protection against HIV disease progression in untreated HIV-seropositive individuals has been linked to immunodominant HLA-B*27:05- restricted CD8* T-cell responses toward the conserved Gag KK10.
In this study, Adland et al. aimed to study the impact of the 3 amino acid differences between HLA-B*27:05 and the closely related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. They found that both HLA-B*27:02 and HLA-B*27:05 were associated with slower disease progression and lower viral loads. However, the effect of HLA-B*27:02 appeared to be consistently stronger than that of HLAB*27:05. In contrast to HLA-B*27:05, the immunodominant HIV-specific HLA-B*27:02-restricted CD8+ T-cell response is to a Nef epitope. Analysis of autologous virus sequences showed that in HLA-B*27:02-positive subjects, all CD8+ T-cell responses impose selection pressure on the virus, whereas in HLA-B*27:05-positive subjects, there is no Nef mediated selection pressure.
These findings indicate that the immunodominant HLA-B*27:02-restricted Nef response adds to protection mediated by the Gag and Pol specificities that dominate anti-HIV CD8+ T-cell activity in HLA-B*27:05-positive subjects.