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).
Author Info: (1) Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland. (2) Institute of Microbiology, ETH Zürich, Zurich, Switzerland. (3) Biozentr
Author Info: (1) Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland. (2) Institute of Microbiology, ETH Zürich, Zurich, Switzerland. (3) Biozentrum, University of Basel, Basel, Switzerland. (4) Experimental Systems Immunology, Max Planck Institute of Biochemistry, Munich, Germany. (5) Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany. (6) Integrated Research Training Group (IRTG) Medical Epigenetics, Collaborative Research Centre 992, Freiburg, Germany.
(7) Institute of Innate Immunity, Department of Systems Immunology and Proteomics, Medical Faculty, University of Bonn, Bonn, Germany. (8) DZIF - German Center for Infection Research, Satellite Center Freiburg, Freiburg, Germany. (9) CIBSS - Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University, Freiburg, Germany. (10) RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany (11) Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Munich, Germany. (12) Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland. roger.geiger@irb.usi.ch.
