|Title||Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Ranasinghe S, Cutler S, Davis I, Lu R, Soghoian DZ, Qi Y, Sidney J, Kranias G, Flanders MD, Lindqvist M, Kuhl B, Alter G, Deeks SG, Walker BD, Gao X, Sette A, Carrington M, Streeck H|
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.
|Alternate Journal||Nat. Med.|
Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control.