Elevated Expression Impairs HIV Control Through Inhibition of NKG2A-expressing Cells

Overview

Journal Science

Specialty Science

Date 2018 Jan 6

PMID 29302013

Citations 91

Authors

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 Haas

Thumbi Ndungu

Philip Goulder

Peter Parham

Bruce D Walker

Jonathan M Carlson

Mary Carrington

Affiliations

Soon will be listed here.

Abstract

The highly polymorphic human leukocyte antigen () locus encodes cell surface proteins that are critical for immunity. 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 levels confer poorer control of HIV. Elevated 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. haplotypes that favor NKG2A-mediated NK cell licensing (i.e., education) exacerbate the deleterious effect of high 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.

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