Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells

Veron Ramsuran, Vivek Naranbhai, Amir Horowitz, Ying Qi, Maureen P. Martin, Yuko Yuki, Xiaojiang Gao, Victoria Walker-Sperling, Gregory Q. Del Prete, Douglas K. Schneider, Jeffrey D. Lifson, Jacques Fellay, Steven G. Deeks, Jeffrey N. Martin, James J. Goedert, Steven M. Wolinsky, Nelson L. Michael, Gregory D. Kirk, Susan Buchbinder, David HaasThumbi Ndung'u, Philip Goulder, Peter Parham, Bruce D. Walker, Jonathan M. Carlson, Mary Carrington*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

The 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 9763 HIV-infected individuals 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 (i.e., 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.

Original languageEnglish (US)
Pages (from-to)86-90
Number of pages5
JournalScience
Volume359
Issue number6371
DOIs
StatePublished - Jan 5 2018

ASJC Scopus subject areas

  • General

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