Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes

Gavin C. Preston, Linda V. Sinclair, Aneesa Kaskar, Jens L. Hukelmann, Maria Navarro, Isabel Ferrero, H. Robson MacDonald, Victoria H. Cowling, Doreen A. Cantrell (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

115 Citations (Scopus)


Myc controls the metabolic reprogramming that supports effector T cell differentiation. The expression of Myc is regulated by the T cell antigen receptor (TCR) and pro-inflammatory cytokines such as interleukin-2 (IL-2). We now show that the TCR is a digital switch for Myc mRNA and protein expression that allows the strength of the antigen stimulus to determine the frequency of T cells that express Myc. IL-2 signalling strength also directs Myc expression but in an analogue process that fine-tunes Myc quantity in individual cells via post-transcriptional control of Myc protein. Fine-tuning Myc matters and is possible as Myc protein has a very short half-life in T cells due to its constant phosphorylation by glycogen synthase kinase 3 (GSK3) and subsequent proteasomal degradation. We show that Myc only accumulates in T cells exhibiting high levels of amino acid uptake allowing T cells to match Myc expression to biosynthetic demands. The combination of digital and analogue processes allows tight control of Myc expression at the population and single cell level during immune responses.

Original languageEnglish
Pages (from-to)2008-2024
Number of pages17
JournalEMBO Journal
Issue number15
Publication statusPublished - 4 Aug 2015


  • Cytokine signals
  • Metabolism
  • Myc
  • T lymphocytes
  • TCR signals

ASJC Scopus subject areas

  • Molecular Biology
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Neuroscience


Dive into the research topics of 'Single cell tuning of Myc expression by antigen receptor signal strength and interleukin-2 in T lymphocytes'. Together they form a unique fingerprint.

Cite this