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

S Ranasinghe, S Cutler, I Davis, R Lu, DZ Soghoian… - Nature medicine, 2013 - nature.com
S Ranasinghe, S Cutler, I Davis, R Lu, DZ Soghoian, Y Qi, J Sidney, G Kranias, MD Flanders…
Nature medicine, 2013nature.com
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 …
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.
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