1. Computational and Systems Biology
  2. Immunology and Inflammation
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Stimulation strength controls the rate of initiation but not the molecular organization of TCR-induced signalling

  1. Claire Y Ma
  2. John C Marioni  Is a corresponding author
  3. Gillian M Griffiths  Is a corresponding author
  4. Arianne C Richard  Is a corresponding author
  1. University of Cambridge, United Kingdom
  2. Wellcome Trust Sanger Institute, United Kingdom
Research Article
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Cite this article as: eLife 2020;9:e53948 doi: 10.7554/eLife.53948

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.

Article and author information

Author details

  1. Claire Y Ma

    Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4244-7535
  2. John C Marioni

    Wellcome Trust Sanger Institute, Hinxton, United Kingdom
    For correspondence
    marioni@ebi.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9092-0852
  3. Gillian M Griffiths

    Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    gg305@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0434-5842
  4. Arianne C Richard

    Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    acr62@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.

Funding

Wellcome (103930,100140,217100)

  • Gillian M Griffiths

Wellcome (204017/Z/16/Z)

  • Claire Y Ma

Cancer Research UK (A17197)

  • John C Marioni

Medical Research Council (MR/P014178/1)

  • Arianne C Richard

Addenbrooke's Charitable Trust, Cambridge University Hospitals (23/17 A (ii))

  • Claire Y Ma

European Molecular Biology Organization

  • John C Marioni

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Animal experimentation: Experiments were carried out under Project Licence PPL 70/8590. This research has been regulated under the Animals (Scientific Procedures) Act 1986 Amendment Regulations 2012 following ethical review by the University of Cambridge Animal Welfare and Ethical Review Body (AWERB).

Reviewing Editor

  1. Michael L Dustin, University of Oxford, United Kingdom

Publication history

  1. Received: November 25, 2019
  2. Accepted: May 14, 2020
  3. Accepted Manuscript published: May 15, 2020 (version 1)

Copyright

© 2020, Ma et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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