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-2D d. In addition, it binds the polysaccharide fucoidan, consistent with its C-type lectin homology and the hypothesis that Ly-49A interacts with carbohydrates on D d. Herein, however, we demonstrate that Ly-49A recognizes D d mutants lacking N-glycosylation. Fucoidan competes for binding with anti-Ly-49A antibodies that inhibit Ly-49A–D d interaction, and blocks apparent Ly-49A binding to unglycosylated D d. We confirm that Ly-49A recognizes the α1 and amino-terminal α2 domains of D d by analysis of recombinant H-2K d-H-2D d molecules. These studies indicate that Ly-49A recognizes carbohydrate-independent epitope(s) on D d and suggest that Ly-49A has two distinct ligands, carbohydrate and MHC class I.