Dynamics in protein translation sustaining T cell preparedness

Research output: Contribution to journalJournal articleResearchpeer-review

  • Tobias Wolf
  • Wenjie Jin
  • Giada Zoppi
  • Ian A Vogel
  • Murodzhon Akhmedov
  • Christopher K E Bleck
  • Tim Beltraminelli
  • Jan C Rieckmann
  • Neftali J Ramirez
  • Marco Benevento
  • Samuele Notarbartolo
  • Dirk Bumann
  • Felix Meissner
  • Bodo Grimbacher
  • Mann, Matthias
  • Antonio Lanzavecchia
  • Federica Sallusto
  • Ivo Kwee
  • Roger Geiger

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).

Original languageEnglish
JournalNature Immunology
ISSN1529-2908
DOIs
Publication statusE-pub ahead of print - 6 Jul 2020
Externally publishedYes

ID: 244994465