Nature Immunology Paper by the Sallusto Lab
Dynamics in protein translation sustaining T cell preparedness
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, Matthias Mann, Antonio Lanzavecchia, Federica Sallusto, Ivo Kwee & Roger Geiger
Nature Immunology (2020) volume 21, pages 927–937
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).
Link to paper in external page Nature Immunology