Association of HLA-A*1101 with resistance and B*4006 with susceptibility to HIV and HIV-TB: An in silico aAnalysis of promiscuous T cell epitopes.

Raghavan, S.; Selvaraj, P.; Swaminathan, S.; Narendran, G.

AIDS Research and Human Retroviruses; 2009; 25; 1023-1028.

Abstract: 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 =.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.

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