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MHC class I–deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I–sufficient environment
In MHC class I–deficient hosts, natural killer (NK) cells are hyporesponsive to cross-linking of activation receptors. Functional competence requires engagement of a self–major histocompatability complex (MHC) class I–specific inhibitory receptor, a process referred to as “licensing.” We previously...
Autores principales: | , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947074/ https://www.ncbi.nlm.nih.gov/pubmed/20819924 http://dx.doi.org/10.1084/jem.20100986 |
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author | Elliott, Julie M. Wahle, Joseph A. Yokoyama, Wayne M. |
author_facet | Elliott, Julie M. Wahle, Joseph A. Yokoyama, Wayne M. |
author_sort | Elliott, Julie M. |
collection | PubMed |
description | In MHC class I–deficient hosts, natural killer (NK) cells are hyporesponsive to cross-linking of activation receptors. Functional competence requires engagement of a self–major histocompatability complex (MHC) class I–specific inhibitory receptor, a process referred to as “licensing.” We previously suggested that licensing is developmentally determined in the bone marrow. In this study, we find that unlicensed mature MHC class I–deficient splenic NK cells show gain-of-function and acquire a licensed phenotype after adoptive transfer into wild-type (WT) hosts. Transferred NK cells produce WT levels of interferon-γ after engagement of multiple activation receptors, and degranulate at levels equivalent to WT NK cells upon coincubation with target cells. Only NK cells expressing an inhibitory Ly49 receptor specific for a cognate host MHC class I molecule show this gain-of-function. Therefore, these findings, which may be relevant to clinical bone marrow transplantation, suggest that neither exposure to MHC class I ligands during NK development in the BM nor endogenous MHC class I expression by NK cells themselves is absolutely required for licensing. |
format | Text |
id | pubmed-2947074 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-29470742011-03-27 MHC class I–deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I–sufficient environment Elliott, Julie M. Wahle, Joseph A. Yokoyama, Wayne M. J Exp Med Brief Definitive Report In MHC class I–deficient hosts, natural killer (NK) cells are hyporesponsive to cross-linking of activation receptors. Functional competence requires engagement of a self–major histocompatability complex (MHC) class I–specific inhibitory receptor, a process referred to as “licensing.” We previously suggested that licensing is developmentally determined in the bone marrow. In this study, we find that unlicensed mature MHC class I–deficient splenic NK cells show gain-of-function and acquire a licensed phenotype after adoptive transfer into wild-type (WT) hosts. Transferred NK cells produce WT levels of interferon-γ after engagement of multiple activation receptors, and degranulate at levels equivalent to WT NK cells upon coincubation with target cells. Only NK cells expressing an inhibitory Ly49 receptor specific for a cognate host MHC class I molecule show this gain-of-function. Therefore, these findings, which may be relevant to clinical bone marrow transplantation, suggest that neither exposure to MHC class I ligands during NK development in the BM nor endogenous MHC class I expression by NK cells themselves is absolutely required for licensing. The Rockefeller University Press 2010-09-27 /pmc/articles/PMC2947074/ /pubmed/20819924 http://dx.doi.org/10.1084/jem.20100986 Text en © 2010 Elliott et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Brief Definitive Report Elliott, Julie M. Wahle, Joseph A. Yokoyama, Wayne M. MHC class I–deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I–sufficient environment |
title | MHC class I–deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I–sufficient environment |
title_full | MHC class I–deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I–sufficient environment |
title_fullStr | MHC class I–deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I–sufficient environment |
title_full_unstemmed | MHC class I–deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I–sufficient environment |
title_short | MHC class I–deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I–sufficient environment |
title_sort | mhc class i–deficient natural killer cells acquire a licensed phenotype after transfer into an mhc class i–sufficient environment |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947074/ https://www.ncbi.nlm.nih.gov/pubmed/20819924 http://dx.doi.org/10.1084/jem.20100986 |
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