Ramsuran, VeronNaranbhai, VivekHorowitz, AmirQi, YingMartin, MaureenYuki, YukoGao, XiaojiangFellay, JacquesDeeks, StevenMartin, Jeffrey N.Goedert, JamesWolinsky, StevenMichael, NelsonKirk, GregoryBuchbinder, SusanHaas, DavidNdung’u, ThumbiGoulder, PhilipParham, PeterWalker, BruceCarlson, Jonathan M.Carrington, Mary2022-08-31Ramsuran, Veron, Vivek Naranbhai, Amir Horowitz, Ying Qi, Maureen P. Martin, Yuko Yuki, Xiaojiang Gao, Jacques Fellay, Steven G. Deeks, Jeffrey N. Martin, James J. Goedert, Steven M. Wolinsky, Nelson L. Michael, Gregory D. Kirk, Susan Buchbinder, David Haas, Thumbi Ndung’u, Philip Goulder, Peter Parham, Bruce D. Walker, Jonathan M. Carlson and Mary Carrington. "Elevated HLA-A expression impairs HIV control through inhibition of Natural Killer cells." Science, 2017.0036-8075https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37373124The highly polymorphic human leukocyte antigen (HLA) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide binding preference. Analysis of 9,763 HIV infected subjects from 21 cohorts shows that higher HLA-A levels confer poorer control of HIV. Elevated HLA-A expression provides enhanced levels of an HLA-A derived signal peptide that specifically binds and determines expression levels of HLA-E, the ligand for the inhibitory NKG2A Natural Killer (NK) cell receptor. HLA-B haplotypes that favor NKG2A-mediated NK cell licensing/education exacerbate the deleterious effect of high HLA-A on HIV control, consistent with NKG2A-mediated inhibition impairing NK cell clearance of HIV-infected targets. Therapeutic blockade of HLA-E:NKG2A interaction may yield benefit in HIV disease.en-USHLA-AexpressionNKG2AHIVnatural killer celllicensingeducationJournal Article2017-05-0420172022-08-31