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Nat Med. 2013 Jul;19(7):930-3. doi: 10.1038/nm.3229. Epub 2013 Jun 23.

Association of HLA-DRB1-restricted CD4⁺ T cell responses with HIV immune control.

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  • 1Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts, USA.

Abstract

The contribution of HLA class II-restricted CD4(+) T cell responses to HIV immune control is poorly defined. Here, we delineated previously uncharacterized peptide-DRB1 restrictions in functional assays and analyzed the host genetic effects of HLA-DRB1 alleles on HIV viremia in a large cohort of HIV controllers and progressors. We found distinct stratifications in the effect of HLA-DRB1 alleles on HIV viremia, with HLA-DRB1*15:02 significantly associated with low viremia and HLA-DRB1*03:01 significantly associated with high viremia. Notably, a subgroup of HLA-DRB1 variants linked with low viremia showed the ability to promiscuously present a larger breadth of peptides with lower functional avidity when compared to HLA-DRB1 variants linked with high viremia. Our data provide systematic evidence that HLA-DRB1 variant expression has a considerable impact on the control of HIV replication, an effect that seems to be mediated primarily by the protein specificity of CD4(+) T cell responses to HIV Gag and Nef.

PMID:
23793098
[PubMed - indexed for MEDLINE]
PMCID:
PMC3974408
Free PMC Article
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