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Volume 9 Supplement 2

AIDS Vaccine 2012

The HIV-1 protective -35SNP effect in Caucasians is CD8 T cell mediated

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Previous studies in Caucasians have observed that a single nucleotide polymorphism 35kb upstream of the HLA-C gene (-35SNP) associates with control of HIV-1 viral load set-point and cell surface expression of HLA-C. HIV-1 selectively downregulates HLA-A and HLA-B but not HLA-C, via the action of the Nef protein. Thus it has been speculated that higher cell surface HLA-C expression results in a stronger HLA-C-restricted T cell response which might play a role in the control of HIV-1 replication in individuals with the protective -35C variant. However, HLA-C-restricted CD8 T cell responses are relatively weak and we could find no difference in functional HLA-C-restricted CD8 T cell activity measured by IFN-γ ELISPOT assay, according to -35SNP genotype. Therefore, we aimed to examine if there is any correlation between total CD8 T cell function and the -35SNP.


The viral suppression assay, which involves directly infecting autologous CD4 T cells with primary HIV-1 strains and co-culturing with autologous CD8 T cells, was used as a surrogate for immune control in vivo. The CD8 T cells from 46 antiretroviral therapy naïve HIV-1 infected Caucasians were assessed using this assay.


When CD8 T cell antiviral activity was grouped according to -35SNP genotype, the -35CC group possessed significantly higher CD8 T cell antiviral activity than the -35TT group (p=0.0151; Mann-Whitney). Protective HLA-B alleles were always in linkage disequilibrium with HLA-C alleles that are in linkage disequilibrium with the -35C allele. Similarly risk HLA-B alleles were in linkage disequilibrium with HLA-C alleles that are in linkage disequilibrium with the -35T allele.


In conclusion, the protective -35SNP effect in HIV-1 disease is mediated through CD8 T cells. However, the -35SNP may simply be a marker for protective and risk HLA-B alleles.

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Correspondence to T Corrah.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Linkage Disequilibrium
  • High Cell Surface
  • Viral Suppression Assay