Dynamics in protein translation sustaining T cell preparedness.
Tobias WolfWenjie JinGiada ZoppiIan A VogelMurodzhon AkhmedovChristopher K E BleckTim BeltraminelliJan C RieckmannNeftali J RamirezMarco BeneventoSamuele NotarbartoloDirk BumannRüdiger KleinBodo GrimbacherMatthias MannAntonio LanzavecchiaFederica SallustoIvo KweeRoger GeigerPublished in: Nature immunology (2020)
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 ).
Keyphrases
- immune response
- binding protein
- bone mineral density
- hiv infected
- protein protein
- transcription factor
- endothelial cells
- public health
- small molecule
- quality improvement
- room temperature
- mass spectrometry
- toll like receptor
- postmenopausal women
- atomic force microscopy
- big data
- deep learning
- inflammatory response
- induced pluripotent stem cells
- quantum dots
- ionic liquid
- aqueous solution