Journal article
Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1
WF Garcia-Beltran, A Hölzemer, G Martrus, AW Chung, Y Pacheco, CR Simoneau, M Rucevic, PA Lamothe-Molina, T Pertel, TE Kim, H Dugan, G Alter, J Dechanet-Merville, S Jost, M Carrington, M Altfeld
Nature Immunology | NATURE PUBLISHING GROUP | Published : 2016
DOI: 10.1038/ni.3513
Abstract
The activating natural killer (NK)-cell receptor KIR3DS1 has been linked to the outcome of various human diseases, including delayed progression of disease caused by human immunodeficiency virus type 1 (HIV-1), yet a ligand that would account for its biological effects has remained unknown. We screened 100 HLA class I proteins and found that KIR3DS1 bound to HLA-F, a result we confirmed biochemically and functionally. Primary human KIR3DS1 + NK cells degranulated and produced antiviral cytokines after encountering HLA-F and inhibited HIV-1 replication in vitro. Activation of CD4 + T cells triggered the transcription and surface expression of HLA-F mRNA and HLA-F protein, respectively, and in..
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Awarded by Broad Institute
Funding Acknowledgements
We thank C. Korner and A. Crespo for advice and discussions; D. Campana (St. Jude Children's Research Hospital) for K562 cells expressing mbIL-15 and CD137L; C. Brander (Ragon Institute of MGH, MIT, and Harvard) for 721.221 cells transduced to express HLA; J. Strominger (Harvard University) for 721.221-HLA-G cells; F. Zhang (Broad Institute of MIT and Harvard) for the lentiCas9-Blast plasmid; L. Ferreira (Harvard University) and T. Meissner (Harvard University) for beta<INF>2</INF>m-targeting single-guide RNA plasmid; and the Ragon Institute Flow Cytometry Core and Virology Core for support and assistance. Supported by the US National Institutes of Health (R01-AI067031-08 and P01-AI104715; F31AI116366 to W.F.G.-B.; the Intramural Research Program, Frederick National Lab, Center for Cancer Research), the National Institute of General Medical Sciences (T32GM007753), the Ragon Institute of MGH, MIT and Harvard, the Frederick National Laboratory for Cancer Research (HHSN261200800001E), the Heinrich-Pette Institute-Leibniz Institute for Experimental Virology (Program Area Antiviral Targets and Strategies) and the German Center for Infection Research. The content is solely the responsibility of the authors and does not necessarily represent the official views or policies of the National Institute of General Medical Sciences, the National Institutes of Health, or the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.