CTL-mediated immune evasion in hiv viraemic controllers and non-controllers

Abstract

Objective: To compare T cell response and to identify the mechanism of escape in HIV-infected volunteers. Methods: HIV-infected volunteers (CD4>450 cells/µL) were enrolled from the anonymous clinic. Volunteers were classified into two groups based on HIV plasma viral load; viraemic controllers (VC) (VL<2000 cp/mL) and non-controllers (NC) (VL>2000 cp/mL). EDTA-whole blood was collected and determined the response against Gag p24 by IFNγ ELISpot assay. Population sequencing within the Gag p24 region was performed to identify escape mutations. Results: Demographic data [age, gender, sexual preference and the presence of protective alleles (HLA-B27, -B57 and –B58)] between VC (n=23) and NC (n=41) were no statistical significance. IFNγ-secreting cells response against Gag p24 as determining by ELISpot assay revealed that some volunteers could not respond to epitopes which are restricted by their HLA alleles (termed as non-responder). The HLA-B27-KK10 non-responders contain HLA polymorphism, HLA-B2706 which accommodates different amino acid with HLA-B2704 and HLA-B2705. The HLA-B57-TW10 and QW9, non-responders did not respond because escape mutation (T242N and T3S, respectively) was found within non-responders’ sequences. Interestingly, HLA-A11-AK11 epitope at the amino acid level was not different among responders and non-responders. Codon usages were subsequently compared and it was found that at the C-terminal position (K; Lysine) preferred different codons for translating to lysine. AAG codon is more preferable in AK11-responders while AAA codon is preferred in AK11 non-responders. In conclusion, these findings may contribute to better knowledge on HIV pathogenesis and the way to improve vaccine efficacy in the future.