The association of MHC class I proteins with the 2B4 receptor inhibits self-killing of human NK cells.
The killing activity of NK cells is carried out by several activating NK receptors, which includes NKp46, NKp44, NKp30, NKp80, NKG2D, and 2B4. The ligands of these receptors are either self-derived, pathogen-derived, stress-induced ligands or tumor ligands. Importantly, none of these killer ligands are expressed on NK cells and thus self-killing of NK cells is prevented. A notable exception with this regard, is the ligand of the 2B4 receptor. This unusual receptor can exert both activating and inhibiting signals; however, in human NK cells, it serves mainly as an activating receptor. The ligand of 2B4 is CD48 and in contrast to the ligands of all the other NK activating receptors, CD48 is also present on NK cells. Thus, NK cells might be at risk for self-killing that is mediated via the 2B4-CD48 interaction. In this study, we identify a novel mechanism that prevents this self-killing as we show that the association of the MHC class I proteins with the 2B4 receptor, both present on NK cells, results in the attenuation of the 2B4-mediated self-killing of NK cells.
Betser-Cohen
Gili
G
The Lautenberg Center for General and Tumor Immunology, The Institute for Medical Research Israel Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Mizrahi
Saar
S
Elboim
Moran
M
Alsheich-Bartok
Osnat
O
Mandelboim
Ofer
O
D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D000071178:CD48 Antigen; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D015536:Down-Regulation / Q000276:immunology*; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000276:immunology; D000071176:Signaling Lymphocytic Activation Molecule Family
D015703:Antigens, CD; C084093:CD244 protein, human; D000071178:CD48 Antigen; C000604065:CD48 protein, human; C000604066:Cd48 protein, mouse; D006131:Growth Inhibitors; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family