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Mechanistic Target of Rapamycin Complex 1/S6 Kinase 1 Signals Influence T Cell Activation Independently of Ribosomal

Robert J Salmond1, Rebecca J Brownlie1, Oded Meyuhas2

  • 1Institute of Immunology and Infection Research, Ashworth Laboratories, University of Edinburgh, Edinburgh EH9 3FL, United Kingdom; and.

Journal of Immunology (Baltimore, Md. : 1950)
|October 11, 2015
PubMed

Insights

Phosphorylation of ribosomal protein S6 (rpS6) is not required for T cell activation, proliferation, or differentiation. The mechanistic target of rapamycin (mTOR) complex 1-S6 kinase 1 (S6K1) pathway regulates T cell activation independently of rpS6 phosphorylation.

Area of Science:

  • Immunology
  • Cellular Metabolism
  • Molecular Biology

Background:

  • T cell activation triggers metabolic changes crucial for growth and differentiation.
  • Mechanistic target of rapamycin (mTOR) integrates signaling pathways regulating T cell metabolism.
  • Downstream effectors of mTOR in T cells remain poorly understood.

Purpose of the Study:

  • To investigate the role of ribosomal protein S6 (rpS6) phosphorylation as an effector of mTOR function in T cells.
  • To determine the necessity of rpS6 phosphorylation for T cell development, growth, proliferation, and differentiation.

Main Methods:

  • Utilized knockin and T cell receptor (TCR) transgenic mouse models.
  • Assessed T cell responses in vitro and in vivo.
  • Examined the effects of rapamycin and an S6 kinase 1 (S6K1)-specific inhibitor.

Main Results:

  • rpS6 phosphorylation was found to be dispensable for T cell development, growth, proliferation, and differentiation.
  • rpS6 knockin mice exhibited normal sensitivity to mTOR inhibitors (rapamycin and S6K1 inhibitor).
  • T cell activation and proliferation were not impaired in the absence of rpS6 phosphorylation.

Conclusions:

  • The mechanistic target of rapamycin (mTOR) complex 1-S6 kinase 1 (S6K1) axis is critical for T cell activation.
  • mTORC1-S6K1 signaling regulates T cell activation independently of its capacity to phosphorylate rpS6.
  • These findings redefine the downstream signaling events regulated by mTOR in T cells.

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