Quantitative analysis of how Myc controls T cell proteomes and metabolic pathways during T cell activation
- 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.
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OT1 T cell activation time courseProteomeXchange, PXD016443.
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Single-cell RNA sequencing of OT-I CD8+ T cells after stimulation with different affinity ligandsArrayExpress identifier: E-MTAB-6051.
Article and author information
Author details
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.
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.
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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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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