Cytoskeletal Control of Antigen-Dependent T Cell Activation.

Actin Cytoskeleton / immunology Humans Jurkat Cells Lymphocyte Activation Receptors, Antigen, T-Cell / immunology Signal Transduction / immunology T-Lymphocytes / cytology
T cell activation TCR cluster TFM actin dynamics immunological synapse mechanosensation mechanosensitivity

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
19 03 2019
Historique:
received: 11 12 2017
revised: 06 08 2018
accepted: 20 02 2019
entrez: 21 3 2019
pubmed: 21 3 2019
medline: 30 4 2020
Statut: ppublish

Résumé

Cytoskeletal actin dynamics is essential for T cell activation. Here, we show evidence that the binding kinetics of the antigen engaging the T cell receptor influences the nanoscale actin organization and mechanics of the immune synapse. Using an engineered T cell system expressing a specific T cell receptor and stimulated by a range of antigens, we found that the peak force experienced by the T cell receptor during activation was independent of the unbinding kinetics of the stimulating antigen. Conversely, quantification of the actin retrograde flow velocity at the synapse revealed a striking dependence on the antigen unbinding kinetics. These findings suggest that the dynamics of the actin cytoskeleton actively adjusted to normalize the force experienced by the T cell receptor in an antigen-specific manner. Consequently, tuning actin dynamics in response to antigen kinetics may thus be a mechanism that allows T cells to adjust the lengthscale and timescale of T cell receptor signaling.

Identifiants

DOI: 10.1016/j.celrep.2019.02.074 PMID: 30893608 PMC: PMC6426652
pubmed: 30893608
pii: S2211-1247(19)30253-0
doi: 10.1016/j.celrep.2019.02.074
pmc: PMC6426652
pii:
doi:

Substances chimiques

Receptors, Antigen, T-Cell 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3369-3379.e5

Subventions

Organisme : Medical Research Council
ID : MC_PC_15002
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U137884181
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C57744/A22057
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_1201/15
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1000800
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_15060
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 212343/Z/18/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 091911
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 107457
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_16082
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12010/9
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0800158
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12010/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00008/1
Pays : United Kingdom
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : Medical Research Council
ID : MR/K01577X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0501975
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00008/9
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 11331
Pays : United Kingdom

Informations de copyright

Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

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Auteurs

Huw Colin-York (H)

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK.

Yousef Javanmardi (Y)

Department of Mechanical Engineering, University College London, London WC1E 7JE, UK.

Mark Skamrahl (M)

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK.

Sudha Kumari (S)

Koch Institute of Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Veronica T Chang (VT)

MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.

Satya Khuon (S)

Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.

Aaron Taylor (A)

Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.

Teng-Leong Chew (TL)

Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.

Eric Betzig (E)

Janelia Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, VA 20147, USA.

Emad Moeendarbary (E)

Department of Mechanical Engineering, University College London, London WC1E 7JE, UK; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

Vincenzo Cerundolo (V)

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK.

Christian Eggeling (C)

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK.

Marco Fritzsche (M)

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Headley Way, Oxford OX3 9DS, UK; Kennedy Institute for Rheumatology, University of Oxford, Roosevelt Drive, Oxford OX3 7LF, UK. Electronic address: marco.fritzsche@rdm.ox.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Cellules › Structures cellulaires › Espace intracellulaire › Cytoplasme › Structures cytoplasmiques › Cytosquelette › Cytosquelette d'actine › Cytoskeletal Control of Antigen-Dependent T...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Cytoskeletal Control of Antigen-Dependent T...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Cellules Jurkat › Cytoskeletal Control of Antigen-Dependent T...
questionsmedicales.fr › Phénomènes du système immunitaire › Activation des lymphocytes › Cytoskeletal Control of Antigen-Dependent T...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux antigènes › Récepteurs aux antigènes des cellules T › Cytoskeletal Control of Antigen-Dependent T...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Cytoskeletal Control of Antigen-Dependent T...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Cytoskeletal Control of Antigen-Dependent T...