We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Association of HLA-DRB1-restricted CD4<sup>+</sup> T cell responses with HIV immune control.
- Authors
Ranasinghe, Srinika; Cutler, Sam; Davis, Isaiah; Lu, Richard; Soghoian, Damien Z; Qi, Ying; Sidney, John; Kranias, Gregory; Flanders, Michael D; Lindqvist, Madelene; Kuhl, Bjorn; Alter, Galit; Deeks, Steven G; Walker, Bruce D; Gao, Xiaojiang; Sette, Alessandro; Carrington, Mary; Streeck, Hendrik
- 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.
- Publication
Nature Medicine, 2013, Vol 19, Issue 7, p930
- ISSN
1078-8956
- Publication type
Academic Journal
- DOI
10.1038/nm.3229