Control of HIV-1 by multiple immunodominant HIV-1-specific CD8+ T cells in HIV-1-infected Japanese individuals

Abstract

Background Previous studies of the comprehensive analysis of HIV-1specific CTL responses in Caucasian and African cohorts demonstrated the association of the CTL responses to HIV-1 Gag protein with the control of HIV-1 replication. However, such analysis in Asian cohorts has not been reported. In the present study, we performed the comprehensive analysis of CD8 + T cell responses against 11-mer overlapping HIV-1 Nef, Gag, and Pol peptides in 401 chronically HIV-1 clade B-infected treatment-naive Japanese individuals. Methods The CD8 + T cell responses to cocktails of the peptides were evaluated by measuring IFN-g-producing CD8 + T cells by using ELISPOT assay. Results To clarify CTLs which control HIV-1 infection in this cohort, we statistically analyzed differences of viral load and CD4 counts between responders to each peptide cocktail in each HLA + individuals and non-responders using two-tailed Mann-Whitney’s test. We found that several HLA alleles were significantly correlated with low viral load and high CD4 counts in the responses to 5 Nef, 10 Gag, or 16 Pol cocktails. In these cocktails, we identified 2 Nef, 12 Gag and 7 Pol CTL epitopes restricted by 9 HLA alleles. The breadth of CTL responses to these epitopes was significantly associated with low viral load (p=1.7x10 -10 ) and high CD4 counts (p=4.1x10 -13 ). The total magnitude of responses to the epitopes was also