title: The human 2B4 and NTB-A receptors bind the influenza viral hemagglutinin and co-stimulate NK cell cytotoxicity.
abstract: Natural Killer (NK) cells are critical in the defense against viruses in general and against influenza in particular. We previously demonstrated that the activating NK cell receptor NKp46 is involved in the killing of influenza-virus infected cells through its interaction with viral hemagglutinin (HA). Furthermore, the recognition by NKp46 and consequent elimination of influenza infected cells were determined to be sialic-acid dependent. Here, we show that the human co-activating receptors 2B4 and NTB-A directly recognize the viral HA protein and co-stimulate killing by NK cells. We demonstrate that the 2B4/NTB-A-HA interactions require the sialylation of these receptors, and we identified the binding sites mediating these interactions. We also show that the virus counters these interactions through its neuraminidase (NA) protein. These results emphasize the critical role played by NK cells in eliminating influenza, a significant cause of worldwide morbidity and mortality.
authors.affiliation: The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem, Israel.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Duev-Cohen
authors.affiliation: The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem, Israel.
authors.forename: Yotam
authors.initials: Y
authors.lastname: Bar-On
authors.affiliation: The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem, Israel.
authors.forename: Ariella
authors.initials: A
authors.lastname: Glasner
authors.affiliation: The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Berhani
authors.affiliation: The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Ophir
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Francesca
authors.initials: F
authors.lastname: Levi-Schaffer
authors.affiliation: Central Virology Laboratory, Ministry of Health, Public Health Services, Chaim Sheba Medical Center, Ramat-Gan, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Mandelboim
authors.affiliation: The Lautenberg Center of General and Tumor Immunology, The Hebrew University Hadassah Medical School, IMRIC, Jerusalem, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Mandelboim
mesh_terms: D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D000071176:Signaling Lymphocytic Activation Molecule Family / Q000276:immunology*
chemical_list: C084093:CD244 protein, human; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C000604060:SLAMF6 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family
keywords: 2B4; NK; NKp46; NTB-A; influenza