Cutting edge: dominance by an MHC-independent inhibitory receptor compromises NK killing of complex targets.
Inhibitory receptors that recognize MHC class I molecules regulate NK cell responses and self-tolerance. Recent evidence indicates that self-ligands not present in the MHC locus also can modulate NK function. In this study, we show that an inhibitory receptor that recognizes an MHC-independent ligand is over expressed in SHIP(-/-) mice at all stages of NK development and differentiation. Overexpression of this receptor compromises key cytolytic NK functions, including killing of allogeneic, tumor, and viral targets. These results further demonstrate the critical role that SHIP plays in regulation of the NK receptor repertoire and show that regulation of MHC-independent inhibitory receptors is crucial for NK recognition and cytolysis of complex targets.
Wahle
Joseph A
JA
Department of Interdisciplinary Oncology, H. Lee Moffitt Comprehensive Cancer Center and Research Institute, University of South Florida, Tampa, FL 33612, USA.
Paraiso
Kim H T
KH
Costello
Amy L
AL
Goll
Emily L
EL
Sentman
Charles L
CL
Kerr
William G
WG
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000950:Antigens, Ly / Q000502:physiology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D015536:Down-Regulation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D000072181:Inositol Polyphosphate 5-Phosphatases; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D037181:Lectins, C-Type / Q000502:physiology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055630:Receptors, NK Cell Lectin-Like; D055607:Receptors, Natural Killer Cell; D015398:Signal Transduction / Q000276:immunology; D000071176:Signaling Lymphocytic Activation Molecule Family; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D000950:Antigens, Ly; C490007:Cd244a protein, mouse; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D055607:Receptors, Natural Killer Cell; D000071176:Signaling Lymphocytic Activation Molecule Family; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases