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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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| Jezik: | English |
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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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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)
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| title_short |
Activating Ly-49d and Inhibitory Ly-49a Natural Killer Cell Receptors Demonstrate Distinct Requirements for Interaction with H2-D(d)
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| title_full |
Activating Ly-49d and Inhibitory Ly-49a Natural Killer Cell Receptors Demonstrate Distinct Requirements for Interaction with H2-D(d)
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| title_fullStr |
Activating Ly-49d and Inhibitory Ly-49a Natural Killer Cell Receptors Demonstrate Distinct Requirements for Interaction with H2-D(d)
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| title_full_unstemmed |
Activating Ly-49d and Inhibitory Ly-49a Natural Killer Cell Receptors Demonstrate Distinct Requirements for Interaction with H2-D(d)
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| 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 |
| _version_ |
1760521953458782208 |