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MTP regulated by an alternate promoter is essential for NKT cell development
Microsomal triglyceride transfer protein (MTP), an endoplasmic reticulum lipid transfer protein critical for apolipoprotein B (apoB) secretion, regulates CD1d antigen presentation. We identified MTP variant 1 (MTPv1), a novel splice variant of mouse MTP, by polymerase chain reaction and Northern ana...
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2137905/ https://www.ncbi.nlm.nih.gov/pubmed/17312007 http://dx.doi.org/10.1084/jem.20062006 |
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author | Dougan, Stephanie K. Rava, Paul Hussain, M. Mahmood Blumberg, Richard S. |
author_facet | Dougan, Stephanie K. Rava, Paul Hussain, M. Mahmood Blumberg, Richard S. |
author_sort | Dougan, Stephanie K. |
collection | PubMed |
description | Microsomal triglyceride transfer protein (MTP), an endoplasmic reticulum lipid transfer protein critical for apolipoprotein B (apoB) secretion, regulates CD1d antigen presentation. We identified MTP variant 1 (MTPv1), a novel splice variant of mouse MTP, by polymerase chain reaction and Northern analysis in non–apoB-secreting tissues, including thymocytes and antigen-presenting cells (APCs). Edman degradation of MTPv1 isolated from transfected cells revealed three unique residues; however, recombinant MTP and MTPv1 had an equivalent protein disulfide isomerase association, subcellular localization, triglyceride transfer, phospholipid transfer, response to inhibitors, and ability to support apoB secretion. MTP and MTPv1 efficiently transferred phosphatidylethanolamine to CD1d in vitro. NKT cells fail to develop in fetal thymic organ culture (FTOC) treated with MTP antagonists. MTP-inhibited FTOCs produced negligible numbers of CD1d tetramer–positive cells and exhibited marked defects in IL-4 production upon stimulation with anti-CD3 or α-galactosylceramide–pulsed APCs. CD1d expression on CD4(+)CD8(+) FTOC cells was unaffected by MTP inhibition. Thus, our results demonstrate that MTPv1 in thymocytes is critical to NKT cell development. We hypothesize that, when MTP is inactive, CD1d traffics to the cell surface and presents no lipid or a lipid that is incapable of mediating NKT cell selection and/or is refractory to lysosomal editing. |
format | Text |
id | pubmed-2137905 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21379052007-12-13 MTP regulated by an alternate promoter is essential for NKT cell development Dougan, Stephanie K. Rava, Paul Hussain, M. Mahmood Blumberg, Richard S. J Exp Med Articles Microsomal triglyceride transfer protein (MTP), an endoplasmic reticulum lipid transfer protein critical for apolipoprotein B (apoB) secretion, regulates CD1d antigen presentation. We identified MTP variant 1 (MTPv1), a novel splice variant of mouse MTP, by polymerase chain reaction and Northern analysis in non–apoB-secreting tissues, including thymocytes and antigen-presenting cells (APCs). Edman degradation of MTPv1 isolated from transfected cells revealed three unique residues; however, recombinant MTP and MTPv1 had an equivalent protein disulfide isomerase association, subcellular localization, triglyceride transfer, phospholipid transfer, response to inhibitors, and ability to support apoB secretion. MTP and MTPv1 efficiently transferred phosphatidylethanolamine to CD1d in vitro. NKT cells fail to develop in fetal thymic organ culture (FTOC) treated with MTP antagonists. MTP-inhibited FTOCs produced negligible numbers of CD1d tetramer–positive cells and exhibited marked defects in IL-4 production upon stimulation with anti-CD3 or α-galactosylceramide–pulsed APCs. CD1d expression on CD4(+)CD8(+) FTOC cells was unaffected by MTP inhibition. Thus, our results demonstrate that MTPv1 in thymocytes is critical to NKT cell development. We hypothesize that, when MTP is inactive, CD1d traffics to the cell surface and presents no lipid or a lipid that is incapable of mediating NKT cell selection and/or is refractory to lysosomal editing. The Rockefeller University Press 2007-03-19 /pmc/articles/PMC2137905/ /pubmed/17312007 http://dx.doi.org/10.1084/jem.20062006 Text en Copyright © 2007, 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/). |
spellingShingle | Articles Dougan, Stephanie K. Rava, Paul Hussain, M. Mahmood Blumberg, Richard S. MTP regulated by an alternate promoter is essential for NKT cell development |
title | MTP regulated by an alternate promoter is essential for NKT cell development |
title_full | MTP regulated by an alternate promoter is essential for NKT cell development |
title_fullStr | MTP regulated by an alternate promoter is essential for NKT cell development |
title_full_unstemmed | MTP regulated by an alternate promoter is essential for NKT cell development |
title_short | MTP regulated by an alternate promoter is essential for NKT cell development |
title_sort | mtp regulated by an alternate promoter is essential for nkt cell development |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2137905/ https://www.ncbi.nlm.nih.gov/pubmed/17312007 http://dx.doi.org/10.1084/jem.20062006 |
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