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

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

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

Author(s) -

Veron Ramsuran,

Vivek Naranbhai,

Amir Horowitz,

Qi Ying,

Maureen P. Martin,

Yuko Yuki,

Xiaojiang Gao,

Victoria E. 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 W. Haas,

Thumbi Ndung’u,

Philip Goulder,

Peter Parham,

Bruce D. Walker,

Jonathan M. Carlson,

Mary Carrington

Publication year - 2018

Publication title -

science

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 12.556

H-Index - 1186

eISSN - 1095-9203

pISSN - 0036-8075

DOI - 10.1126/science.aam8825

Subject(s) - human leukocyte antigen , immunology , biology , immune system , virus , immunity , viral load , virology , antigen , human immunodeficiency virus (hiv) , gene expression , gene , genetics

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.

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