![]() Thus, T cells face a tradeoff between minimizing their metabolic activity while sustaining a maximally prepared state for rapid execution of the activation program. However, following activation T cells need to rapidly undergo a substantial reprogramming to mount an effective response 5. While surveying for cognate antigen, quiescent T cells maintain a cellular program with minimal energy expenditure 3, 4. Naïve T cells may remain inactive for many years in a spore-like state 1, 2. Resting T cells patrol the body in a quiescent yet poised state, prepared to mount a robust immune response to pathogenic threats such as infectious diseases and cancers. 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 ( Introduction These components were rapidly engaged following stimulation, promoting an immediate translational and glycolytic switch to ramp up the T cell activation program. Furthermore, naïve T cells maintained a surprisingly large number of idling ribosomes as well as 242 repressed mRNA species and a reservoir of glycolytic enzymes. Our datasets uncovered that transcription factors maintaining T cell quiescence had constitutively high turnover, which facilitated their depletion upon activation. Using a pulsed SILAC approach, we investigated the dynamics of mRNA translation kinetics and protein turnover in human naïve and activated T cells. In response to pathogenic threats, naïve T cells rapidly transition from a quiescent to activated state, yet the underlying mechanisms are incompletely understood.
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