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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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Glavni autori: Nakamura, Mary C., Hayashi, Shigenari, Niemi, Eréne C., Ryan, James C., Seaman, William E.
Format: Članak
Jezik:English
Izdano: The Rockefeller University Press 2000
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Online pristup:https://ncbi.nlm.nih.gov/pmc/articles/PMC2193226/
https://ncbi.nlm.nih.gov/pubmed/10934233
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spelling pubmed-21932262008-04-16 Activating Ly-49d and Inhibitory Ly-49a Natural Killer Cell Receptors Demonstrate Distinct Requirements for Interaction with H2-D(d) Nakamura, Mary C. Hayashi, Shigenari Niemi, Eréne C. Ryan, James C. Seaman, William E. J Exp Med Brief Definitive Report 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) α(1) helix or the α(2) helix abrogated Ly-49D–mediated cytotoxicity, but these changes had no significant effect on Ly-49A–dependent inhibition. Each of three α(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. The Rockefeller University Press 2000-08-07 /pmc/articles/PMC2193226/ /pubmed/10934233 Text en © 2000 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
institution US National Library of Medicine
collection PubMed Central
language English
format Article
topic Brief Definitive Report
spellingShingle Brief Definitive Report
Nakamura, Mary C.
Hayashi, Shigenari
Niemi, Eréne C.
Ryan, James C.
Seaman, William E.
Activating Ly-49d and Inhibitory Ly-49a Natural Killer Cell Receptors Demonstrate Distinct Requirements for Interaction with H2-D(d)
description 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) α(1) helix or the α(2) helix abrogated Ly-49D–mediated cytotoxicity, but these changes had no significant effect on Ly-49A–dependent inhibition. Each of three α(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.
author Nakamura, Mary C.
Hayashi, Shigenari
Niemi, Eréne C.
Ryan, James C.
Seaman, William E.
author_facet Nakamura, Mary C.
Hayashi, Shigenari
Niemi, Eréne C.
Ryan, James C.
Seaman, William E.
author_sort Nakamura, Mary C.
title Activating Ly-49d and Inhibitory Ly-49a Natural Killer Cell Receptors Demonstrate Distinct Requirements for Interaction with H2-D(d)
title_short Activating Ly-49d and Inhibitory Ly-49a Natural Killer Cell Receptors Demonstrate Distinct Requirements for Interaction with H2-D(d)
title_full Activating Ly-49d and Inhibitory Ly-49a Natural Killer Cell Receptors Demonstrate Distinct Requirements for Interaction with H2-D(d)
title_fullStr Activating Ly-49d and Inhibitory Ly-49a Natural Killer Cell Receptors Demonstrate Distinct Requirements for Interaction with H2-D(d)
title_full_unstemmed Activating Ly-49d and Inhibitory Ly-49a Natural Killer Cell Receptors Demonstrate Distinct Requirements for Interaction with H2-D(d)
title_sort activating ly-49d and inhibitory ly-49a natural killer cell receptors demonstrate distinct requirements for interaction with h2-d(d)
publisher The Rockefeller University Press
publisher_facet The Rockefeller University Press
publishDate 2000
url https://ncbi.nlm.nih.gov/pmc/articles/PMC2193226/
https://ncbi.nlm.nih.gov/pubmed/10934233
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