The lectin-like NK cell receptor Ly-49A recognizes a carbohydrate-independent epitope on its MHC class I ligand.
The mouse NK inhibitory Ly-49A receptor specifically interacts with a peptide-induced conformational determinant on its MHC class I ligand, H-2Dd. In addition, it binds the polysaccharide fucoidan, consistent with its C-type lectin homology and the hypothesis that Ly-49A interacts with carbohydrates on Dd. Herein, however, we demonstrate that Ly-49A recognizes Dd mutants lacking N-glycosylation. Fucoidan competes for binding with anti-Ly-49A antibodies that inhibit Ly-49A-Dd interaction, and blocks apparent Ly-49A binding to unglycosylated Dd. We confirm that Ly-49A recognizes the alpha1 and amino-terminal alpha2 domains of Dd by analysis of recombinant H-2Kd-H-2Dd molecules. These studies indicate that Ly-49A recognizes carbohydrate-independent epitope(s) on Dd and suggest that Ly-49A has two distinct ligands, carbohydrate and MHC class I.
Matsumoto
N
N
Howard Hughes Medical Institute, Rheumatology Division, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Ribaudo
R K
RK
Abastado
J P
JP
Margulies
D H
DH
Yokoyama
W M
WM
D000818:Animals; D000950:Antigens, Ly; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes; D006023:Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006031:Glycosylation; D006183:H-2 Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D037102:Lectins / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008024:Ligands; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D055630:Receptors, NK Cell Lectin-Like
D000950:Antigens, Ly; D002352:Carrier Proteins; D000939:Epitopes; D006023:Glycoproteins; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D064532:Histocompatibility Antigen H-2D; D037102:Lectins; D037181:Lectins, C-Type; D008024:Ligands; D008565:Membrane Proteins; D011134:Polysaccharides; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; C007789:fucoidan