Antigen receptor control of methionine metabolism in T cells.

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Sinclair, LV; Howden, AJ; Brenes, A; Spinelli, L; Hukelmann, JL; Macintyre, AN; Liu, X; Thomson, S; Taylor, PM; Rathmell, JC; Locasale, JW; Lamond, AI; Cantrell, DA

Published Date

  • March 27, 2019

Published In

Volume / Issue

  • 8 /

PubMed ID

  • 30916644

Pubmed Central ID

  • 30916644

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.44210

Language

  • eng

Conference Location

  • England