The early proximal αβ TCR signalosome specifies thymic selection outcome through a quantitative protein interaction network.

Animals CD3 Complex / genetics Cell Differentiation / immunology Mice Mice, Inbred C57BL Mice, Transgenic Pneumonia, Pneumocystis / immunology Protein Interaction Maps / immunology Proteomics / methods Receptors, Antigen, T-Cell, alpha-beta / metabolism Signal Transduction / immunology Theilovirus / immunology Thymocytes / immunology Thymus Gland / metabolism

Journal

Science immunology
ISSN: 2470-9468
Titre abrégé: Sci Immunol
Pays: United States
ID NLM: 101688624

Informations de publication

Date de publication:
15 02 2019
Historique:
received: 14 10 2016
accepted: 17 01 2019
entrez: 17 2 2019
pubmed: 17 2 2019
medline: 9 4 2020
Statut: ppublish

Résumé

During αβ T cell development, T cell antigen receptor (TCR) engagement transduces biochemical signals through a protein-protein interaction (PPI) network that dictates dichotomous cell fate decisions. It remains unclear how signal specificity is communicated, instructing either positive selection to advance cell differentiation or death by negative selection. Early signal discrimination might occur by PPI signatures differing qualitatively (customized, unique PPI combinations for each signal), quantitatively (graded amounts of a single PPI series), or kinetically (speed of PPI pathway progression). Using a novel PPI network analysis, we found that early TCR-proximal signals distinguishing positive from negative selection appeared to be primarily quantitative in nature. Furthermore, the signal intensity of this PPI network was used to find an antigen dose that caused a classic negative selection ligand to induce positive selection of conventional αβ T cells, suggesting that the quantity of TCR triggering was sufficient to program selection outcome. Because previous work had suggested that positive selection might involve a qualitatively unique signal through CD3δ, we reexamined the block in positive selection observed in CD3δ

Identifiants

DOI: 10.1126/sciimmunol.aal2201 PMID: 30770409 PMC: PMC7252671
pubmed: 30770409
pii: 4/32/eaal2201
doi: 10.1126/sciimmunol.aal2201
pmc: PMC7252671
mid: NIHMS1026700
pii:
doi:

Substances chimiques

CD3 Complex 0
CD3delta antigen 0
Receptors, Antigen, T-Cell, alpha-beta 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NICHD NIH HHS
ID : U54 HD083091
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007386
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI097187
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM103841
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007425
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM065841
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS094765
Pays : United States

Informations de copyright

Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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Auteurs

Steven C Neier (SC)

Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN, USA.
ORCID: 0000-0003-2742-8608

Alejandro Ferrer (A)

Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA.
ORCID: 0000-0002-4883-3023

Katelynn M Wilton (KM)

Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN, USA.
Medical Scientist Training Program, Mayo Clinic College of Medicine, Rochester, MN, USA.
ORCID: 0000-0001-5060-8899

Stephen E P Smith (SEP)

Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA.
ORCID: 0000-0003-4180-573X

April M H Kelcher (AMH)

Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Mayo Graduate School, Mayo Clinic College of Medicine, Rochester, MN, USA.
Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA.
ORCID: 0000-0002-9665-2921

Kevin D Pavelko (KD)

Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA.
ORCID: 0000-0001-7555-1315

Jenna M Canfield (JM)

Molecular Pathogenesis and Therapeutics PhD Graduate Program, University of Missouri, Columbia, MO, USA.
ORCID: 0000-0001-5980-7392

Tessa R Davis (TR)

Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA.
ORCID: 0000-0003-0660-7850

Robert J Stiles (RJ)

Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA.
ORCID: 0000-0001-8794-0019

Zhenjun Chen (Z)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia.
ORCID: 0000-0003-1205-683X

James McCluskey (J)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia.
ORCID: 0000-0002-8597-815X

Scott R Burrows (SR)

QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
School of Medicine, University of Queensland, Brisbane, Queensland 4006, Australia.

Jamie Rossjohn (J)

Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
ORCID: 0000-0002-2020-7522

Deanne M Hebrink (DM)

Thoracic Diseases Research Unit, Division of Pulmonary Critical Care and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.

Eva M Carmona (EM)

Thoracic Diseases Research Unit, Division of Pulmonary Critical Care and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.

Andrew H Limper (AH)

Thoracic Diseases Research Unit, Division of Pulmonary Critical Care and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA.

Dietmar J Kappes (DJ)

Blood Cell Development and Cancer Keystone, Immune Cell Development and Host Defense Program, Fox Chase Cancer Center, Philadelphia, PA, USA.

Peter J Wettstein (PJ)

Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Department of Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA.

Aaron J Johnson (AJ)

Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA.
ORCID: 0000-0002-7921-484X

Larry R Pease (LR)

Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA.

Mark A Daniels (MA)

Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO, USA.
Department of Surgery, School of Medicine, University of Missouri, Columbia, MO, USA.
ORCID: 0000-0002-5175-9901

Claudia Neuhauser (C)

University of Minnesota Informatics Institute, Minneapolis, MN, USA.
ORCID: 0000-0001-8932-675X

Diana Gil (D)

Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO, USA. schruma@health.missouri.edu gilpagesd@health.missouri.edu.
Department of Surgery, School of Medicine, University of Missouri, Columbia, MO, USA.
Department of Bioengineering, College of Engineering, University of Missouri, Columbia, MO, USA.
ORCID: 0000-0003-1744-3484

Adam G Schrum (AG)

Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia, MO, USA. schruma@health.missouri.edu gilpagesd@health.missouri.edu.
Department of Surgery, School of Medicine, University of Missouri, Columbia, MO, USA.
Department of Bioengineering, College of Engineering, University of Missouri, Columbia, MO, USA.
ORCID: 0000-0001-9276-1859

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › The early proximal αβ TCR signalosome...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes T › Antigènes CD3 › The early proximal αβ TCR signalosome...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Différenciation cellulaire › The early proximal αβ TCR signalosome...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › The early proximal αβ TCR signalosome...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › The early proximal αβ TCR signalosome...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › The early proximal αβ TCR signalosome...
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumonie à Pneumocystis › The early proximal αβ TCR signalosome...
questionsmedicales.fr › Métabolisme › Voies et réseaux métaboliques › Cartes d'interactions protéiques › The early proximal αβ TCR signalosome...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Protéomique › The early proximal αβ TCR signalosome...
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 › Récepteur lymphocytaire T antigène, alpha-bêta › The early proximal αβ TCR signalosome...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › The early proximal αβ TCR signalosome...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Picornaviridae › Cardiovirus › Theilovirus › The early proximal αβ TCR signalosome...
questionsmedicales.fr › Cellules › Thymocytes › The early proximal αβ TCR signalosome...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Système lymphatique › Tissu lymphoïde › Thymus (glande) › The early proximal αβ TCR signalosome...