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Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain

The CD3ε and ζ cytoplasmic domains of the T cell receptor bind to the inner leaflet of the plasma membrane (PM), and a previous nuclear magnetic resonance structure showed that both tyrosines of the CD3ε immunoreceptor tyrosine-based activation motif partition into the bilayer. Electrostatic interac...

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Autores principales: Gagnon, Etienne, Schubert, David A., Gordo, Susana, Chu, H. Hamlet, Wucherpfennig, Kai W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526357/
https://www.ncbi.nlm.nih.gov/pubmed/23166358
http://dx.doi.org/10.1084/jem.20120790
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author Gagnon, Etienne
Schubert, David A.
Gordo, Susana
Chu, H. Hamlet
Wucherpfennig, Kai W.
author_facet Gagnon, Etienne
Schubert, David A.
Gordo, Susana
Chu, H. Hamlet
Wucherpfennig, Kai W.
author_sort Gagnon, Etienne
collection PubMed
description The CD3ε and ζ cytoplasmic domains of the T cell receptor bind to the inner leaflet of the plasma membrane (PM), and a previous nuclear magnetic resonance structure showed that both tyrosines of the CD3ε immunoreceptor tyrosine-based activation motif partition into the bilayer. Electrostatic interactions between acidic phospholipids and clusters of basic CD3ε residues were previously shown to be essential for CD3ε and ζ membrane binding. Phosphatidylserine (PS) is the most abundant negatively charged lipid on the inner leaflet of the PM and makes a major contribution to membrane binding by the CD3ε cytoplasmic domain. Here, we show that TCR triggering by peptide–MHC complexes induces dissociation of the CD3ε cytoplasmic domain from the plasma membrane. Release of the CD3ε cytoplasmic domain from the membrane is accompanied by a substantial focal reduction in negative charge and available PS in TCR microclusters. These changes in the lipid composition of TCR microclusters even occur when TCR signaling is blocked with a Src kinase inhibitor. Local changes in the lipid composition of TCR microclusters thus render the CD3ε cytoplasmic domain accessible during early stages of T cell activation.
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spelling pubmed-35263572013-06-17 Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain Gagnon, Etienne Schubert, David A. Gordo, Susana Chu, H. Hamlet Wucherpfennig, Kai W. J Exp Med Article The CD3ε and ζ cytoplasmic domains of the T cell receptor bind to the inner leaflet of the plasma membrane (PM), and a previous nuclear magnetic resonance structure showed that both tyrosines of the CD3ε immunoreceptor tyrosine-based activation motif partition into the bilayer. Electrostatic interactions between acidic phospholipids and clusters of basic CD3ε residues were previously shown to be essential for CD3ε and ζ membrane binding. Phosphatidylserine (PS) is the most abundant negatively charged lipid on the inner leaflet of the PM and makes a major contribution to membrane binding by the CD3ε cytoplasmic domain. Here, we show that TCR triggering by peptide–MHC complexes induces dissociation of the CD3ε cytoplasmic domain from the plasma membrane. Release of the CD3ε cytoplasmic domain from the membrane is accompanied by a substantial focal reduction in negative charge and available PS in TCR microclusters. These changes in the lipid composition of TCR microclusters even occur when TCR signaling is blocked with a Src kinase inhibitor. Local changes in the lipid composition of TCR microclusters thus render the CD3ε cytoplasmic domain accessible during early stages of T cell activation. The Rockefeller University Press 2012-12-17 /pmc/articles/PMC3526357/ /pubmed/23166358 http://dx.doi.org/10.1084/jem.20120790 Text en © 2012 Gagnon 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 Article
Gagnon, Etienne
Schubert, David A.
Gordo, Susana
Chu, H. Hamlet
Wucherpfennig, Kai W.
Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain
title Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain
title_full Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain
title_fullStr Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain
title_full_unstemmed Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain
title_short Local changes in lipid environment of TCR microclusters regulate membrane binding by the CD3ε cytoplasmic domain
title_sort local changes in lipid environment of tcr microclusters regulate membrane binding by the cd3ε cytoplasmic domain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526357/
https://www.ncbi.nlm.nih.gov/pubmed/23166358
http://dx.doi.org/10.1084/jem.20120790
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