The impact of HLA-Cw*12:02 on control of HIV-1 infection
© Koyanagi et al; licensee BioMed Central Ltd. 2012
Published: 13 September 2012
Previous studies have demonstrated that higher HLA-C expression, which is determined through a single nucleotide polymorphism 35 kb upstream and the variation within the 3’ untranslated region of the HLA-C locus, associate with slow progression of HIV-1-infected disease. Although HLA-C plays important roles in presenting antigens to CTLs or a ligand for inhibitory killer cell Ig-like receptors (KIR), the role of HLA-C-restricted CTL and NK cells in the control of HIV-1 is still unclear. Our recent study of chronically HIV-1 infected Japanese cohort showed that the HLA-B*52:01-Cw*12:02 haplotype was significantly associated with lower viral load. In this study, we investigated whether HLA-Cw*12:02-restricted CTLs or NK cells via KIR have a significant impact on viraemic control.
We sequenced Pol, Gag and Nef from 400 chronically HIV-1 clade B-infected treatment-naïve Japanese individuals and then analyzed amino acid polymorphisms associated with HLA-B*52:01-Cw*12:02 haplotype using Fisher’s exact test. Next we performed intracellular IFNg staining or IFNg ELISPOT assay to detect CTL responses to the peptides including those polymorphisms.
We found 9 amino acid polymorphisms significantly associated with HLA-B*52:01-Cw*12:02 haplotype (p<0.002 q<0.2). By using ICC assay, we identified 2 Cw*12:02-restricted CTL epitopes and 4 B*52:01-restricted ones. Four Cw*12:02-restricted CTL epitopes including previously reported ones were analyzed to investigate the effect of Cw*12:02-restricted CTLs on control of HIV-1. No significant correlation between the responses to these Cw*12:02-restricted epitopes and viral load was found in chronically HIV-1 infected Cw*12:02 positive Japanese individuals.
Those results showed that HLA-Cw*12:02-restrected CTLs have no effect on control of HIV-1 and suggested that HLA-B*52:01-restrected CTLs or Cw*12:02-resticted NK cells control HIV-1 viraemia in Japanese cohort.
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 (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.