The transcription factor IRF4 is essential for TCR affinity–mediated metabolic programming and clonal expansion of T cells Academic Article uri icon

abstract

  • 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.

authors

  • Man, Kevin
  • Miasari, Maria
  • Shi, Wei
  • Xin, Annie
  • Henstridge, Darren C
  • Preston, Simon
  • Pellegrini, Marc
  • Belz, Gabrielle T
  • Smyth, Gordon K
  • Febbraio, Mark A
  • Nutt, Stephen L
  • Kallies, Axel

publication date

  • November 2013