NK Cell Inhibitory Receptor Ly-49C Residues Involved in MHC Class I Binding

• Published in: The Journal of immunology (1950) 2002-01, Vol.168 (2), p.793-800
• Main Authors: Sundback, Jonas, Achour, Adnane, Michaelsson, Jakob, Lindstrom, Hannah, Karre, Klas
• Format: Article
• Language: English
• Subjects: Amino Acid Substitution - genetics; Amino Acid Substitution - immunology; Amino Acids - genetics; Amino Acids - metabolism; Animals; Antibodies, Monoclonal - metabolism; Antigens, Ly; Binding Sites, Antibody - genetics; Cell Line; Crystallography, X-Ray; H-2 Antigens - metabolism; Histocompatibility Antigen H-2D; Humans; killer cell inhibitory receptors; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Lectins, C-Type; Ly-49A antigen; Ly-49C antigen; Medicin och hälsovetenskap; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Models, Molecular; Mutagenesis, Site-Directed; Protein Binding - genetics; Protein Binding - immunology; Receptors, Immunologic - genetics; Receptors, Immunologic - immunology; Receptors, Immunologic - metabolism; Receptors, NK Cell Lectin-Like
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.168.2.793

Mouse NK cells express Ly-49 receptors specific for classical MHC class I molecules. Several of the Ly-49 receptors have been characterized in terms of function and ligand specificity. However, the only Ly-49 receptor-ligand interaction previously described in detail is that between Ly-49A and H-2D(d), as studied by point mutations in the ligand and the crystal structure of the co-complex of these molecules. It is not known whether other Ly-49 receptors bind MHC class I in a similar manner as Ly-49A. Here we have studied the effect of mutations in Ly-49C on binding to the MHC class I molecules H-2K(b), H-2D(b), and H-2D(d). The MHC class I molecules were used as soluble tetramers to stain transiently transfected 293T cells expressing the mutated Ly-49C receptors. Three of nine mutations in Ly-49C led to loss of MHC class I binding. The three Ly-49C mutations that affected MHC binding correspond to Ly-49A residues that are in contact or close to H-2D(d) in the co-crystal, demonstrating that MHC class I binding by Ly-49C is dependent on residues in the same area as that used by Ly-49A for ligand contacts.