Ly-49W, an activating receptor of nonobese diabetic mice with close homology to the inhibitory receptor Ly-49G, recognizes H-2D(k) and H-2D(d).
The diversity and ligand specificity of activating Ly-49 receptors expressed by murine NK cells are largely unknown. We cloned a new Ly-49-activating receptor, expressed by NK cells of the nonobese diabetic mouse strain, which we have designated Ly-49W. Ly-49W is highly related to the known inhibitory receptor Ly-49G in its carbohydrate recognition domain, exhibiting 97.6% amino acid identity in this region. We demonstrate that the 4D11 and Cwy-3 Abs, thought to be Ly-49G specific, also recognize Ly-49W. Rat RNK-16 cells transfected with Ly-49W mediated reverse Ab-dependent cellular cytotoxicity of FcR-positive target cells, indicating that Ly-49W can activate NK-mediated lysis. We further show that Ly-49W is allo-MHC specific: Ly-49W transfectants of RNK-16 only lysed Con A blasts expressing H-2(k) or H-2(d) haplotypes, and Ab-blocking experiments indicated that H-2D(k) and D(d) are ligands for Ly-49W. Ly-49W is the first activating Ly-49 receptor demonstrated to recognize an H-2(k) class I product. Ly-49G and Ly-49W represent a new pair of NK receptors with very similar ligand-binding domains, but opposite signaling functions.
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Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Gong
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Hazes
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D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics / Q000276:immunology; D000950:Antigens, Ly; D001666:Binding Sites, Antibody / Q000235:genetics; D001667:Binding, Competitive / Q000235:genetics / Q000276:immunology; D019556:COS Cells; D003001:Cloning, Molecular; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D006183:H-2 Antigens / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000235:genetics; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D051381:Rats; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D055630:Receptors, NK Cell Lectin-Like; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D037181:Lectins, C-Type; C423703:Ly-49W receptor; C423705:Ly-49W1 receptor; C423704:Ly-49W2 receptor; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D003208:Concanavalin A