A ligand for the murine NK activation receptor Ly-49D: activation of tolerized NK cells from beta 2-microglobulin-deficient mice.
Mouse NK cells express inhibitory NK receptors that recognize target cell MHC class I molecules and activation receptors that are less well defined. The Ly-49D activation receptor on C57BL/6 NK cells recognizes Chinese hamster ovary cells and triggers natural killing. In this study, we demonstrate that a Chinese hamster classical MHC class I molecule is the ligand for Ly-49D in a reporter gene assay system as well as in NK cell killing assays. Ly-49D recognizes the Chinese hamster class I molecule better when it is expressed with Chinese hamster beta(2)-microglobulin (beta(2)m) than murine beta(2)m. However, it is still controversial that Ly-49D recognizes H-2D(d), as we were unable to demonstrate the specificity previously reported. Using this one ligand-one receptor recognition system, function of an NK activation receptor was, for the first time, investigated in NK cells that are tolerized in beta(2)m-deficient mice. Surprisingly, Ly-49D-killing activity against ligand-expressing targets was observed with beta(2)m-deficient mouse NK cells, albeit reduced, even though "tolerized" function of Ly-49D was expected. These results indicate that Ly-49D specifically recognizes the Chinese hamster MHC class I molecule associated with Chinese hamster beta(2)m, and indicate that the Ly-49D NK cell activation receptor is not tolerized in beta(2)m deficiency.
Furukawa
Hiroshi
H
Howard Hughes Medical Institute, Rheumatology Division, Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
Iizuka
Koho
K
Poursine-Laurent
Jennifer
J
Shastri
Nilabh
N
Yokoyama
Wayne M
WM
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D000950:Antigens, Ly; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus / Q000235:genetics / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type; D008024:Ligands; D008213:Lymphocyte Activation / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D051381:Rats; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055630:Receptors, NK Cell Lectin-Like; D000071176:Signaling Lymphocytic Activation Molecule Family; D013045:Species Specificity; D014161:Transduction, Genetic; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000235:genetics*
D015703:Antigens, CD; D000950:Antigens, Ly; C084093:CD244 protein, human; C490008:Cd244 protein, rat; C490007:Cd244a protein, mouse; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D000071176:Signaling Lymphocytic Activation Molecule Family; D001613:beta 2-Microglobulin