HIV T Cell immunology: CD8+ T Cell responses and epitope mapping among thais predominantly infected with HIV-1 subtype ae

Abstract

The role of CD8+ T cells and HLA class I in viral escape and viral control has not been well characterised in clade CRF01_AE and Asian ethnics. We have studied HIV-1 specific CD8+ T cell responses among 240 naive HIV-1 infected Thai individuals with IFN-γ ELISpot assay against a set of 413 overlapping peptides (OLPs) of HIV-1 proteome. We found patients’ CD8 T cells were responsive to the four most common HIV-1 targets including Pol (91%), Gag (87%), Env (83%) and Nef (78%). As has been reported in other ethnic groups and subtypes, Gag-specific CD8+ T cell response was associated with low plasma HIV-RNA level, whereas Env-specific CD8+ T cell response was associated with high plasma HIV-RNA level. HLA-B*1302 and HLA-A*2410 after excluding other known protective alleles were associated with low plasma HIV-RNA level ( p =0.0024 and p = 0.0062, respectively). We then further investigated among 195 HIV-1 CRF01_AE infected Thais, 33 OLPs were identified as potential novel epitopes. Some of these epitopes were further characterised. A novel immunodominant (29% response rate) restricted by HLA-Cw*0102: YI9 (in Gag-p24) which was associated with viral escape. Mutations at P2 (S278X), P4 (V280X) and P5 (S281G) impaired the ELISpot responses, however the P2 anchor S278K mutation had the highest negative impact ( p = 0.0002). We also found two viral control epitopes. The first, RI10 (HIV-protease, previously described in HIV-1 B clade as -B*13 restricted), was found restricted by HLA-A*0203. Interestingly, HLA-A*0203 positive patients with RI10 responders had a significantly lower plasma HIV-RNA level than non-responders ( p = 0.0167). In conclusion, HLA-B*1302 and HLA-A*2410 were associated with low plasma HIV-RNA level. Pol, Gag, Env and Nef are four common HIV targets of CD8 T cells, however, only HIV-1 Gag was found associated with low plasma HIV-RNA level. Three CD8 epitopes: YI9, RI10 and AK11 restricted by HLA-Cw*0102, -A*0203 and -A*1101, respectively, were characterised. RI10 and AK11, but not YI9, were associated with lower plasma HIV-RNA level.