Ly-49P activates NK-mediated lysis by recognizing H-2Dd.
Little is known regarding the ligand specificity of Ly-49 activating receptor subfamily members expressed by NK cells. A new Ly-49 activating receptor related to Ly-49A in its extracellular domain, designated Ly-49P, was recently cloned from 129 strain mice. We independently cloned an apparent allele of Ly-49P expressed by nonobese diabetic and nonobese diabetes-resistant mouse strain NK cells. We found it to be reactive with the A1 Ab thought to recognize a polymorphic epitope expressed only by the Ly-49A inhibitory receptor of the C57BL/6 strain. Rat RNK-16 cells transfected with Ly-49P mediated reverse Ab-dependent cellular cytotoxicity of FcR-positive target cells, indicating that Ly-49P can activate NK-mediated lysis. We determined that RNK-16 lysis of Con A blasts induced by Ly-49P was MHC dependent, resulting in efficient lysis of H-2Dd-bearing targets. We found that the Dd alpha1/alpha2 domain is required for Ly-49P-mediated RNK-16 activation, as determined by exon shuffling and transfection. Thus, Ly-49P is the second activating Ly-49 receptor demonstrated to induce NK cytotoxicity by recognizing a class I MHC molecule.
Silver
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Department of Medical Microbiology and Immunology, Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada.
Gong
D E
DE
Chang
C S
CS
Amrani
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A
Santamaria
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P
Kane
K P
KP
D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics / Q000276:immunology*; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification; D003208:Concanavalin A / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D000939:Epitopes / Q000096:biosynthesis; D005260:Female; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D007106:Immune Sera / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D051381:Rats; D011916:Rats, Inbred F344; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D055630:Receptors, NK Cell Lectin-Like; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism
D000950:Antigens, Ly; D002352:Carrier Proteins; D000939:Epitopes; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007106:Immune Sera; D037181:Lectins, C-Type; C400050:Ly49P receptor; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D003208:Concanavalin A