Association of HLA-DRB1-restricted CD4+ T cell responses with HIV immune control
Deeks, Steven G.
Streeck, HendrikNote: Order does not necessarily reflect citation order of authors.
MetadataShow full item record
CitationRanasinghe, S., S. Cutler, I. Davis, R. Lu, D. Z. Soghoian, Y. Qi, J. Sidney, et al. 2013. “Association of HLA-DRB1-restricted CD4+ T cell responses with HIV immune control.” Nature medicine 19 (7): 930-933. doi:10.1038/nm.3229. http://dx.doi.org/10.1038/nm.3229.
AbstractThe contribution of HLA class II-restricted CD4+ T cell responses to HIV immune control is poorly defined. Here, we delineated novel 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 (n=1085). We found distinct stratifications in the effect of HLA-DRB1 alleles on HIV viremia, with DRB1*15:02 significantly associated with low viremia (P=0.003, q=0.04) and DRB1*03:01 significantly associated with high viremia (P=0.004, q=0.04). Interestingly, a sub-group of HLA-DRB1 alleles linked with low viremia showed the ability to promiscuously present a larger breadth of peptides with lower functional avidity when compared to HLA-DRB1 alleles linked with high viremia (p=0.018). Our data provide systematic evidence that HLA-DRB1 allele expression significantly impacts the durable control of HIV replication, an effect that appears to be mediated primarily by the protein-specificity of HIV-specific CD4+ T cell responses to Gag and Nef.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12152886