Activating Ly-49D and inhibitory Ly-49A natural killer cell receptors demonstrate distinct requirements for interaction with H2-D(d)

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...

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Bibliographic Details
Published in:The Journal of experimental medicine 2000-08, Vol.192 (3), p.447
Main Authors: Nakamura, M C, Hayashi, S, Niemi, E C, Ryan, J C, Seaman, W E
Format: Article
Language:English
Subjects:
Amino Acid Substitution
Animals
Antigens, Ly - immunology
Carrier Proteins - immunology
H-2 Antigens - chemistry
H-2 Antigens - immunology
Histocompatibility Antigen H-2D
Killer Cells, Natural - immunology
Lectins, C-Type
Membrane Glycoproteins - immunology
Membrane Proteins - immunology
Mice
Mutagenesis
Peptides - immunology
Protein Structure, Tertiary
Receptors, Immunologic - immunology
Receptors, NK Cell Lectin-Like
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Summary: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.
ISSN:0022-1007
DOI:10.1084/jem.192.3.447