title: Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1.
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 induced binding of KIR3DS1. HIV-1 infection further increased the transcription of HLA-F mRNA but decreased the binding of KIR3DS1, indicative of a mechanism for evading recognition by KIR3DS1(+) NK cells. Thus, we have established HLA-F as a ligand of KIR3DS1 and have demonstrated cell-context-dependent expression of HLA-F that might explain the widespread influence of KIR3DS1 in human disease.
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Wilfredo F
authors.initials: WF
authors.lastname: Garcia-Beltran
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.|Heinrich-Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.|First Department of Internal Medicine, University Medical Centre Eppendorf, Hamburg, Germany.
authors.forename: Angelique
authors.initials: A
authors.lastname: Hölzemer
authors.affiliation: Heinrich-Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Gloria
authors.initials: G
authors.lastname: Martrus
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Amy W
authors.initials: AW
authors.lastname: Chung
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.|Departamento de Matemáticas, Facultad de Ciencias, Universidad Nuestra Señora del Rosario, Bogotá, Colombia.
authors.forename: Yovana
authors.initials: Y
authors.lastname: Pacheco
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Camille R
authors.initials: CR
authors.lastname: Simoneau
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Marijana
authors.initials: M
authors.lastname: Rucevic
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Lamothe-Molina
authors.affiliation: Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pertel
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Tae-Eun
authors.initials: TE
authors.lastname: Kim
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Haley
authors.initials: H
authors.lastname: Dugan
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Galit
authors.initials: G
authors.lastname: Alter
authors.affiliation: CNRS, UMR 5164, Université de Bordeaux, Bordeaux, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Dechanet-Merville
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Jost
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.|Cancer and Inflammation Program, Laboratory of Experimental Immunology, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
authors.forename: Mary
authors.initials: M
authors.lastname: Carrington
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.|Heinrich-Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Altfeld
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D057131:Immune Evasion; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008213:Lymphocyte Activation; D061251:Primary Cell Culture; D054349:Receptors, KIR3DS1 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D017735:Virus Latency; D014779:Virus Replication
chemical_list: D016207:Cytokines; C062341:HLA-F antigens; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D054349:Receptors, KIR3DS1