Antigen receptor control of methionine metabolism in T cells
- University of Dundee, United Kingdom
- Vanderbilt University, United States
- Duke University, United States
- Vanderbilt Universit, United States
Abstract
Immune activated T lymphocytes modulate the activity of key metabolic pathways to support the transcriptional reprograming and reshaping of cell proteomes that permits effector T cell differentiation. The present study uses high resolution mass spectrometry and metabolic labelling to explore how murine T cells control the methionine cycle to produce methyl donors for protein and nucleotide methylations. We show that antigen receptor engagement controls flux through the methionine cycle and RNA and histone methylations. We establish that the main rate limiting step for protein synthesis and the methionine cycle is control of methionine transporter expression. Only T cells that respond to antigen to upregulate and sustain methionine transport are supplied with methyl donors that permit the dynamic nucleotide methylations and epigenetic reprogramming that drives T cell differentiation. These data highlight how the regulation of methionine transport licenses use of methionine for multiple fundamental processes that drive T lymphocyte proliferation and differentiation.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files, or being submitted to the PRIDE ProteomeXchange consortium.
Article and author information
Author details
Funding
Wellcome (097418/Z/11/Z)
- Doreen A Cantrell
Wellcome (202950/Z/16/Z)
- Doreen A Cantrell
Wellcome (205023/Z/16/Z)
- Doreen A Cantrell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. This work was supported by the Wellcome Trust (Principal Research Fellowship to D.A.C. 097418/Z/11/Z and 205023/Z/16/Z ; Wellcome Trust Equipment Award 202950/Z/16/Z ).
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 licence for submission to the HO. All studies, breeding and maintenance performed in Dundee in compliance with UK Home Office Animals (Scientific Procedures) Act 1986 guidelines. Individual study plans were approved and deemed compliant by the UVS/Named Compliance Officer.
Copyright
© 2019, Sinclair 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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Antigen receptor control of methionine metabolism in T cells
eLife 8:e44210.
https://doi.org/10.7554/eLife.44210
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