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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...

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Detalles Bibliográficos
Autores principales: Elliott, Julie M., Wahle, Joseph A., Yokoyama, Wayne M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2010
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.
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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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