2B4 (CD244)-CD48 interactions provide a novel MHC class I-independent system for NK-cell self-tolerance in mice.
Natural killer (NK) cells must be able to eliminate infected and transformed cells while remaining tolerant of normal cells. NK-cell self-tolerance is thought to be maintained by self-major histocompatibility complex (MHC) class I recognition; however, there are examples where NK cells are not regulated by MHC class I and yet remain self-tolerant. Here, we show that 2B4 (CD244) and CD48 represent a second system for murine NK-cell self-recognition. 2B4 and MHC class I receptors act nonredundantly to inhibit NK lysis of syngeneic tumor cells. NK cells from beta2 microglobulin (beta2m)-deficient mice and NK cells that lack expression of self-MHC-binding inhibitory receptors are inhibited by 2B4. Moreover, we provide the first in vivo evidence for MHC-independent NK self-recognition in a bone marrow rejection assay. These data suggest that NK-cell self-tolerance can be mediated by molecules other than MHC.
McNerney
Megan E
ME
Department of Pathology, University of Chicago, 5841 S Maryland Ave, S-315 MC3083, Chicago, IL 60637, USA. mcnerney@midway.uchicago.edu
Guzior
Dustin
D
Kumar
Vinay
V
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000276:immunology; D000071178:CD48 Antigen; D003602:Cytotoxicity, Immunologic; D006084:Graft Rejection / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000276:immunology / Q000473:pathology; D011971:Receptors, Immunologic / Q000276:immunology*; D017634:Self Tolerance; D000071176:Signaling Lymphocytic Activation Molecule Family; D014185:Transplantation, Isogeneic; D001613:beta 2-Microglobulin / Q000172:deficiency
D015703:Antigens, CD; D000071178:CD48 Antigen; C490007:Cd244a protein, mouse; C000604066:Cd48 protein, mouse; D015395:Histocompatibility Antigens Class I; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D001613:beta 2-Microglobulin