During immune responses, T cells are subject to clonal competition, which leads to the predominant expansion of high-affinity clones; however, there is little understanding of how this process is controlled. We found here that the transcription factor IRF4 was induced in a manner dependent on affinity for the T cell antigen receptor (TCR) and acted as a dose-dependent regulator of the metabolic function of activated T cells. IRF4 regulated the expression of key molecules required for the aerobic glycolysis of effector T cells and was essential for the clonal expansion and maintenance of effector function of antigen-specific CD8⁺ T cells. Thus, IRF4 is an indispensable molecular 'rheostat' that 'translates' TCR affinity into the appropriate transcriptional programs that link metabolic function with the clonal selection and effector differentiation of T cells.

Item Type:	Refereed Article
Keywords:	beta actin, CD8 antigen, Hermes antigen, interferon regulatory factor 4, interleukin 2 receptor alpha, T lymphocyte receptor, animal cell, antigen specificity, article, binding affinity, CD8+ T lymphocyte, cell expansion, cell metabolism, glycolysis
Research Division:	Biological Sciences
Research Group:	Biochemistry and cell biology
Research Field:	Signal transduction
Objective Division:	Health
Objective Group:	Clinical health
Objective Field:	Clinical health not elsewhere classified
UTAS Author:	Henstridge, DC (Dr Darren Henstridge)
ID Code:	133345
Year Published:	2013
Web of Science® Times Cited:	253
Deposited By:	Health Sciences
Deposited On:	2019-06-24
Last Modified:	2019-07-23
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