title: Evidence that the KIR2DS5 gene codes for a surface receptor triggering natural killer cell function.
abstract: In this study, after immunization with NK cells from a KIR2DS5(+) donor and screening on cell transfectants expressing different members of the killer immunoglobulin-like receptor (KIR) family, we generated a mAb, DF200, reacting with several KIR2D receptors including KIR2DL1/L2/L3, KIR2DS1/S2 and KIR2DS5. By the analysis of peripheral blood NK cells and in vitro derived NK cell clones, we have demonstrated for the first time that KIR2DS5 is expressed at the cell surface in discrete subsets of NK cells and, after DF200 mAb-mediated engagement, can induce both cytotoxicity and cytokine release. Using co-transfection and co-immunoprecipitation, we found that KIR2DS5 associates with the DAP12 signaling polypeptide. Finally, soluble KIR2DS5-Fc fusion protein does not bind to cell transfectants expressing different HLA-C alleles, suggesting that, if KIR2DS5 does recognize HLA-C molecules, this may only occur in the presence of certain peptides.
authors.affiliation: Dipartimento di Medicina Sperimentale, Università di Genova, Genova, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: Della Chiesa
authors.forename: Elisa
authors.initials: E
authors.lastname: Romeo
authors.forename: Michela
authors.initials: M
authors.lastname: Falco
authors.forename: Mirna
authors.initials: M
authors.lastname: Balsamo
authors.forename: Raffaella
authors.initials: R
authors.lastname: Augugliaro
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Cristina
authors.initials: C
authors.lastname: Bottino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Massimo
authors.initials: M
authors.lastname: Vitale
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D015236:HLA-C Antigens / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000502:physiology*; D008565:Membrane Proteins / Q000502:physiology; D054340:Receptors, KIR / Q000235:genetics / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D015236:HLA-C Antigens; D008565:Membrane Proteins; D054340:Receptors, KIR; C110546:TYROBP protein, human; D007371:Interferon-gamma