title: The mouse NKR-P1B:Clr-b recognition system is a negative regulator of innate immune responses.
abstract: NKR-P1B is a homodimeric type II transmembrane C-type lectinlike receptor that inhibits natural killer (NK) cell function upon interaction with its cognate C-type lectin-related ligand, Clr-b. The NKR-P1B:Clr-b interaction represents a major histocompatibility complex class I (MHC-I)-independent missing-self recognition system that monitors cellular Clr-b levels. We have generated NKR-P1B(B6)-deficient (Nkrp1b(-/-)) mice to study the role of NKR-P1B in NK cell development and function in vivo. NK cell inhibition by Clr-b is abolished in Nkrp1b(-/-) mice, confirming the inhibitory nature of NKR-P1B(B6). Inhibitory receptors also promote NK cell tolerance and responsiveness to stimulation; hence, NK cells expressing NKR-P1B(B6) and Ly49C/I display augmented responsiveness to activating signals vs NK cells expressing either or none of the receptors. In addition, Nkrp1b(-/-) mice are defective in rejecting cells lacking Clr-b, supporting a role for NKR-P1B(B6) in MHC-I-independent missing-self recognition of Clr-b in vivo. In contrast, MHC-I-dependent missing-self recognition is preserved in Nkrp1b(-/-) mice. Interestingly, spontaneous myc-induced B lymphoma cells may selectively use NKR-P1B:Clr-b interactions to escape immune surveillance by wild-type, but not Nkrp1b(-/-), NK cells. These data provide direct genetic evidence of a role for NKR-P1B in NK cell tolerance and MHC-I-independent missing-self recognition.
authors.affiliation: Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada;
authors.forename: Mir Munir A
authors.initials: MM
authors.lastname: Rahim
authors.affiliation: Department of Immunology, University of Toronto, Sunnybrook Research Institute, Toronto, ON, Canada;
authors.forename: Peter
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada;
authors.forename: Amelia N
authors.initials: AN
authors.lastname: Mottashed
authors.affiliation: Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada; College of Applied Medical Sciences, Taibah University, Madinah Munawwarah, Kingdom of Saudi Arabia;
authors.forename: Ahmad Bakur
authors.initials: AB
authors.lastname: Mahmoud
authors.affiliation: Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada;
authors.forename: Midhun J
authors.initials: MJ
authors.lastname: Thomas
authors.affiliation: Transgenic Core Facility, Clinical Research Institute of Montreal, Montreal, QC, Canada;
authors.forename: Qinzhang
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Institute of Cell and Molecular Biosciences, The Medical School, Newcastle, United Kingdom;
authors.forename: Colin G
authors.initials: CG
authors.lastname: Brooks
authors.affiliation: Prince Henry's Institute, Monash Medical Centre, Clayton, VIC, Australia; and.
authors.forename: Vicky
authors.initials: V
authors.lastname: Kartsogiannis
authors.affiliation: Prince Henry's Institute, Monash Medical Centre, Clayton, VIC, Australia; and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Gillespie
authors.affiliation: Department of Immunology, University of Toronto, Sunnybrook Research Institute, Toronto, ON, Canada;
authors.forename: James R
authors.initials: JR
authors.lastname: Carlyle
authors.affiliation: Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, ON, Canada;
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Makrigiannis
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000502:physiology*; D008024:Ligands; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000502:physiology*
chemical_list: D015395:Histocompatibility Antigens Class I; C527212:Klrb1b protein, mouse; D037181:Lectins, C-Type; D008024:Ligands; D008565:Membrane Proteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; C429003:Ocil protein, mouse