Protective HIV-specific [CD8.sup.+] T cells evade [T.sub.reg] cell suppression

Specific human leukocyte antigens (HLAs), notably HLA-B*27 and HLA-B*57 allele groups, have long been associated with control of HIV-1. Although the majority of HIV-specific [CD8.sup.+] T cells lose proliferative capacity during chronic infection, T cells restricted by HLA-B*27 or HLA-B*57 allele groups do not. Here we show that [CD8.sup.+] T cells restricted by 'protective' HLA allele groups are not suppressed by [T.sub.reg] cells, whereas, within the same individual, T cells restricted by 'nonprotective' alleles are highly suppressed ex vivo. This differential sensitivity of HIV-specific [CD8.sup.+] T cells to [T.sub.reg] cell-mediated suppression correlates with their expression of the inhibitory receptor T cell immunoglobulin domain and mucin domain 3 (Tim-3) after stimulation with their cognate epitopes. Furthermore, we show that HLA-B*27- and HLA-B*57-restricted effectors also evade [T.sub.reg] cell-mediated suppression by directly killing [T.sub.reg] cells they encounter in a granzyme B (GzmB)-dependent manner. This study reg uncovers a previously unknown explanation for why HLA-B*27 and HLA-B*57 allele groups are associated with delayed HIV-1 disease progression.