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

作者：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^*

来源：Nature Medicine, 2013, 19(7): 930-+.

DOI：10.1038/nm.3229

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.

• 出版日期2013-7