Quantitative analysis of how Myc controls T cell proteomes and metabolic pathways during T cell activation

  1. Julia M Marchingo
  2. Linda V Sinclair  Is a corresponding author
  3. Andrew JM Howden
  4. Doreen A Cantrell  Is a corresponding author
  1. University of Dundee, United Kingdom

Abstract

T cell expansion and differentiation are critically dependent on the transcription factor c-Myc (Myc). Herein we use quantitative mass-spectrometry to reveal how Myc controls antigen receptor driven cell growth and proteome restructuring in murine T cells. Analysis of copy numbers per cell of >7000 proteins provides new understanding of the selective role of Myc in controlling the protein machinery that govern T cell fate. The data identify both Myc dependent and independent metabolic processes in immune activated T cells. We uncover that a primary function of Myc is to control expression of multiple amino acid transporters and that loss of a single Myc-controlled amino acid transporter effectively phenocopies the impact of Myc deletion. This study provides a comprehensive map of how Myc selectively shapes T cell phenotypes, revealing that Myc induction of amino acid transport is pivotal for subsequent bioenergetic and biosynthetic programs and licences T cell receptor driven proteome reprogramming.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Raw mass spec data files and MaxQuant analysis files for naïve WT, and TCR activated MycWT, MyccKO, Slc7a5WT and Slc7a5cKO T cells are available on the ProteomeXchange data repository (https://www.ebi.ac.uk/pride/archive/login) and can be accessed with identifier PXD016105. Raw mass spec data files and MaxQuant analysis files for OT-1 TCR time-course data are available on the ProteomeXchange data repository (https://www.ebi.ac.uk/pride/archive/login) and can be accessed with identifier PXD016443.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Julia M Marchingo

    Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8823-9718
  2. Linda V Sinclair

    Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
    For correspondence
    l.v.sinclair@dundee.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1248-7189
  3. Andrew JM Howden

    Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4332-9469
  4. Doreen A Cantrell

    Cell Signalling and Immunology, University of Dundee, Dundee, United Kingdom
    For correspondence
    d.a.cantrell@dundee.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7525-3350

Funding

Wellcome (097418/Z/11/Z)

  • Doreen A Cantrell

Wellcome (205023/Z/16/Z)

  • Doreen A Cantrell

Wellcome (202950/Z/16/Z)

  • Doreen A Cantrell

European Molecular Biology Organization (ALTF 1543-2015)

  • Julia M Marchingo

European Commission (705984)

  • Julia M Marchingo
  • Doreen A Cantrell

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

Reviewing Editor

  1. Ellen A Robey, University of California, Berkeley, United States

Ethics

Animal experimentation: All animal experiments were performed under Project License PPL 60/4488 and P4BD0CE74. The University of Dundee Welfare and Ethical Use of Animals Committee accepted the project license for submission to the Home Office. Mice were bred and maintained in the WTB/RUTG, University of Dundee in compliance with UK Home Office Animals (Scientific Procedures) Act 1986 guidelines.

Version history

  1. Received: November 18, 2019
  2. Accepted: February 4, 2020
  3. Accepted Manuscript published: February 5, 2020 (version 1)
  4. Version of Record published: March 4, 2020 (version 2)

Copyright

© 2020, Marchingo 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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  1. Julia M Marchingo
  2. Linda V Sinclair
  3. Andrew JM Howden
  4. Doreen A Cantrell
(2020)
Quantitative analysis of how Myc controls T cell proteomes and metabolic pathways during T cell activation
eLife 9:e53725.
https://doi.org/10.7554/eLife.53725

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https://doi.org/10.7554/eLife.53725

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