HIV-1-specific CD8+ T cells with different abilities to recognize HIV-1-infected cells in HIV-1-exposed seronegative individuals

The presence of HIV-1-specific CD8⁺ T-cell responses in HIV-1-exposed seronegative (HESN) individuals has been reported, but the details of these T cells have yet to be analyzed. We investigated HIV-1-specific CD8⁺ T-cell responses to 281 17-mer overlapping HIV-1 peptides and six HLA-B*15:02-restricted HIV-1 subtype AE epitope peptides in 370 Vietnamese HESN men who have sex with men (MSM). Analysis of cultured T cells stimulated with these peptides using intracellular cytokine staining (ICS) assay demonstrated HIV-1-specific CD8⁺ T-cell responses in only eight of these HESN-MSM. HLA-restricted CD8⁺ T cells specific for five HIV-1 epitope peptides were identified in five of these individuals by ICS assay and/or assay using HLA multimers. CD8⁺ T cells specific for three HIV-1 peptides (GagHL9, PolSV9, and PolVF9) recognized HIV-1 subtype AE-infected cells, whereas those specific for two HIV-1 peptides did not recognize them. Among CD8⁺ T cells that can recognize HIV-1-infected cells, those specific for two epitopes, GagHL9 and PolSV9, were frequently elicited in HIV-1-infected individuals, whereas PolVF9-specific CD8⁺ T cells were not found in them. These results indicate that two types of HIV-1-specific CD8⁺ T cells were clearly detected in HESN-MSM; they include CD8⁺ T cells specific for the immunodominant or nonimmunodominant HIV-1 epitope peptide that is effectively presented in HIV-1-infected cells and those for the HIV-1 peptide that is very weakly or not presented by HLA class I in HIV-1-infected cells. The present study demonstrated the existence of different HIV-1-specific CD8⁺ T cells that can or cannot recognize HIV-1-infected cells before HIV-1 infection is established.