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Dynamics in protein translation sustaining T cell preparedness

Nat Immunol. 2020 Aug;21(8):927-937. doi: 10.1038/s41590-020-0714-5. Epub 2020 Jul 6.

Abstract

In response to pathogenic threats, naive T cells rapidly transition from a quiescent to an activated state, yet the underlying mechanisms are incompletely understood. Using a pulsed SILAC approach, we investigated the dynamics of mRNA translation kinetics and protein turnover in human naive and activated T cells. Our datasets uncovered that transcription factors maintaining T cell quiescence had constitutively high turnover, which facilitated their depletion following activation. Furthermore, naive T cells maintained a surprisingly large number of idling ribosomes as well as 242 repressed mRNA species and a reservoir of glycolytic enzymes. These components were rapidly engaged following stimulation, promoting an immediate translational and glycolytic switch to ramp up the T cell activation program. Our data elucidate new insights into how T cells maintain a prepared state to mount a rapid immune response, and provide a resource of protein turnover, absolute translation kinetics and protein synthesis rates in T cells ( https://www.immunomics.ch ).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Lymphocyte Activation / physiology*
  • Protein Biosynthesis / immunology*
  • RNA, Messenger / immunology
  • RNA, Messenger / metabolism
  • T-Lymphocytes / immunology*
  • Transcription Factors / immunology
  • Transcription Factors / metabolism

Substances

  • RNA, Messenger
  • Transcription Factors