1. Activating Ly-49d and Inhibitory Ly-49a Natural Killer Cell Receptors Demonstrate Distinct Requirements for Interaction with H2-Dd
- Author
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Nakamura, Mary C, Hayashi, Shigenari, Niemi, Eréne C, Ryan, James C, and Seaman, William E
- Subjects
Underpinning research ,1.1 Normal biological development and functioning ,Amino Acid Substitution ,Animals ,Antigens ,Ly ,Carrier Proteins ,H-2 Antigens ,Histocompatibility Antigen H-2D ,Killer Cells ,Natural ,Lectins ,C-Type ,Membrane Glycoproteins ,Membrane Proteins ,Mice ,Mutagenesis ,Peptides ,Protein Structure ,Tertiary ,Receptors ,Immunologic ,Receptors ,NK Cell Lectin-Like ,natural killer cells ,major histocompatibility complex ,receptors ,cytotoxicity ,rodent ,Medical and Health Sciences ,Immunology - Abstract
The activating Ly-49D receptor and the inhibitory Ly-49A receptor mediate opposing effects on natural killer (NK) cell cytotoxicity after interaction with the same major histocompatibility complex ligand, H2-D(d). To compare Ly-49D and Ly-49A interactions with H2-D(d), we created mutations in H2-D(d) and examined the functional ability of these mutants to activate lysis through Ly-49D or to inhibit lysis through Ly-49A. Specific single amino acid changes in either the H2-D(d) alpha(1) helix or the alpha(2) helix abrogated Ly-49D-mediated cytotoxicity, but these changes had no significant effect on Ly-49A-dependent inhibition. Each of three alpha(2) domain mutations in the floor of the peptide binding groove reduced functional recognition by either Ly-49D or Ly-49A, but all three were required to fully abrogate inhibition by Ly-49A. Our studies indicate that Ly-49D/H2-D(d) interactions require distinct determinants compared with Ly-49A/H2-D(d) interactions. These differences have important implications for the integration of activating and inhibitory signals in NK cells.
- Published
- 2000