Investigating the mechanisms by which naive, quiescent T cells rapidly become activated, Wolf and Jin et al. used a pulsed SILAC approach and identified a small set of transcription factors that were responsible for maintaining quiescence, were rapidly turned over in naive T cells, and hence were rapidly depleted upon activation, facilitating rapid reprogramming. Naive T cells also maintained high numbers of idling ribosomes, repressed mRNA species (most regulated by mTOR), and glycolytic enzymes, which were rapidly engaged upon stimulation. Memory T cells also showed higher protein turnover to support a higher state of preparedness and more rapid responses.
Contributed by Lauren Hitchings
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).