Dynamics in protein translation sustaining T cell preparedness

维持T细胞准备状态的蛋白质翻译动力学

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作者: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 Kw

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 ).

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