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Stimulation strength controls the rate of initiation but not the molecular organization of TCR-induced signalling

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Ma, Claire 

Abstract

Millions of naïve T cells with different TCRs may interact with a peptide-MHC ligand, but very few will activate. Remarkably, this fine control is orchestrated using a limited set of intracellular machinery. It remains unclear whether changes in stimulation strength alter the programme of signalling events leading to T cell activation. Using mass cytometry to simultaneously measure multiple signalling pathways during activation of murine CD8+ T cells, we found a programme of distal signalling events that is shared, regardless of the strength of TCR stimulation. Moreover, the relationship between transcription of early response genes Nr4a1 and Irf8 and activation of the ribosomal protein S6 is also conserved across stimuli. Instead, we found that stimulation strength dictates the rate with which cells initiate signalling through this network. These data suggest that TCR-induced signalling results in a coordinated activation program, modulated in rate but not organization by stimulation strength.

Description

Keywords

CD8 T cells, T cell receptor, computational biology, immunology, inflammation, mass cytometry, mouse, signalling, systems biology, Animals, CD8-Positive T-Lymphocytes, Cells, Cultured, Female, Flow Cytometry, Interferon Regulatory Factors, Kinetics, Ligands, Lymphocyte Activation, Male, Mice, Inbred C57BL, Mice, Transgenic, Nuclear Receptor Subfamily 4, Group A, Member 1, Ovalbumin, Peptide Fragments, Phosphorylation, Receptors, Antigen, T-Cell, Ribosomal Protein S6, Signal Transduction, Single-Cell Analysis

Journal Title

eLife

Conference Name

Journal ISSN

2050-084X
2050-084X

Volume Title

Publisher

eLife Sciences Publications Ltd

Rights

All rights reserved
Sponsorship
Wellcome Trust (103930/Z/14/Z)
Medical Research Council (MR/P014178/1)
Addenbrooke's Charitable Trust (ACT) (Minute 23/17 A (ii))
Wellcome Trust (217100/Z/19/Z)
Cancer Research UK (C14303/A17197)
Wellcome Trust (100140/Z/12/Z)
Wellcome Trust (204017/Z/16/Z)
Medical Research Council (MR/M008975/1)
Wellcome Trust Cancer Research UK Addenbrookes Charitable Trust National Institute for Health Research