Ranasinghe, SrinikaCutler, SamDavis, IsaiahLu, RichardSoghoian, DamienQi, YingSidney, JohnKranias, GregoryFlanders, MichaelLindqvist, MadeleneKuhl, BjornAlter, GalitDeeks, Steven G.Walker, BruceGao, XiaojiangSette, AlessandroCarrington, MaryStreeck, Hendrik2014-05-062013Ranasinghe, 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.3229.1078-8956http://nrs.harvard.edu/urn-3:HUL.InstRepos:12152886The 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.en-USJournal Article2014-05-0610.1038/nm.3229