Ligand interactions by activating and inhibitory Ly-49 receptors.
Natural killer (NK) cells express families of homologous receptors, members of which either activate or inhibit NK cells. We demonstrate that mouse Ly-49D is an activating receptor for the MHC antigen H2-Dd, which is also a ligand for the related inhibitory receptor Ly-49A. To compare and contrast their interactions with class I MHC ligand, we studied each of these receptors expressed in a rat NK-cell hne, RNK-16, for their capacity to recognize wild-type or mutated H2-Dd. Our studies with Ly-49A reveal that functional interaction with H2-Dd depends on residues in the floor of the H2-Dd peptide-binding groove. The recent co-crystal of Ly-49A with H2-Dd indicates that these are not contact residues, thus they may contribute to allelic specificity through conformational changes in H2-Dd. We found that structural requirements for functional recognition of H2-Dd by Ly-49D differ markedly from those for recognition by Ly-49A. We note that H2-Dd expression on certain target cells is not sufficient to activate lysis mediated by Ly-49D, though the additional requirements for functional interaction are not yet identified. Here we review recent studies of Ly-49 receptor ligand specificities and their molecular basis. The functions of these related receptors with opposing functions and shared allospecificity remains unclear.
Nakamura
M C
MC
Department of Medicine, University of California, San Francisco, USA. marynak@itsa.ucsf.edu
Seaman
W E
WE
D000818:Animals; D000950:Antigens, Ly; D002352:Carrier Proteins / Q000378:metabolism; D006224:Cricetinae; D006183:H-2 Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D051381:Rats; D011971:Receptors, Immunologic / Q000378:metabolism*; D055630:Receptors, NK Cell Lectin-Like; D013045:Species Specificity
D000950:Antigens, Ly; D002352:Carrier Proteins; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like