Short communication: association of HLA-A*1101 with resistance and B*4006 with susceptibility to HIV and HIV-TB: an in silico analysis of promiscuous T cell epitopes.

We have shown the association of HLA-A*11 with resistance and HLA-B*40 and -DR2 with susceptibility to HIV and HIV-TB. In the present study, we performed high-resolution subtyping of HLA-A*11 and -B*40 to identify the subtype level association, using the polymerase chain reaction-based sequence-specific oligonucleotide probe method. Underrepresentation of HLA-A*1101 was observed in overall HIV [p(c) = 0.012, OR 0.42 (95% confidence interval (CI) 0.24-0.72)] and HIV(+)TB(+) [p(c) = 0.001, OR 0.18 (95% CI 0.06-0.46)] compared to healthy controls. Significantly higher frequencies of HLA-B*4006 were observed in overall HIV [p = 0.0001, p(c) = 0.004, OR 2.71 (95% CI 1.58-4.75)], HIV(+)TB(-) [p = 0.0003, p(c) = 0.008, OR 2.82 (95% CI 1.56-5.17)], and HIV(+)TB(+) [p = 0.003, p(c) = 0.086, OR 2.56 (95% CI 1.33-4.95)] compared to healthy controls. An in silico analysis of potential T cell epitopes of consensus Gag and Pol sequences of HIV-1 subtype C Indian strains revealed relatively higher number of promiscuous HLA-B40, HLA-DRB1*1501, and -DRB1*1502 (HLA-DR2)-restricted epitopes in contrast to limited numbers of promiscuous binders restricted by HLA-A*1101. The results suggest that HLA-A*1101 may be associated with protection against HIV and the development of TB in HIV patients while HLA-B*4006 may be associated with susceptibility to HIV and TB development in HIV patients. The present study also suggests that the extent of promiscuity of T cell epitopes of HIV-1 subtype C restricted by HLA alleles exerting opposing effects might differ.