Dynamics in protein translation sustaining T cell preparedness
Authors: Giada Zoppi
Tobias Wolf
Neftali J Ramirez
Christopher K E Bleck
Marco Benevento
Jan C Rieckmann
Murodzhon Akhmedov
Bodo Grimbacher
Dirk Bumann
Tim Beltraminelli
Ivo Kwee
Antonio Lanzavecchia
Roger Geiger
Federica Sallusto
Samuele Notarbartolo
Ian A Vogel
Wenjie Jin
Matthias Mann
Felix Meissner
Journal: Nature Immunology (2020)
Discipline: IMMUNOLOGY
Keywords: T cells; mRNA translation kinetics; protein turnover; transcription factors; ribosomes
Affiliations: Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland., Institute of Microbiology, ETH Zürich, Zurich, Switzerland., Biozentrum, University of Basel, Basel, Switzerland., Experimental Systems Immunology, Max Planck Institute of Biochemistry, Munich, Germany., Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany., Integrated Research Training Group (IRTG) Medical Epigenetics, Collaborative Research Centre 992, Freiburg, Germany., Institute of Innate Immunity, Department of Systems Immunology and Proteomics, Medical Faculty, University of Bonn, Bonn, Germany., DZIF - German Center for Infection Research, Satellite Center Freiburg, Freiburg, Germany., CIBSS - Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University, Freiburg, Germany., RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany., Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Munich, Germany., Institute for Research in Biomedicine, Università della Svizzera italiana, Bellinzona, Switzerland. .

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 ). 

Retracted: No

PubPeer comments:
 The acting blot in figure 7B is quite similar to the actin blot that has appeared in five other publications from this group. The resolution is lower, but the features are eerily similar. It is shown as it appeared in the original figure and also enlarged and aligned with two examples of this recurring blot. Five examples are shown in: https: pubpeer.com publications 013834175109D0766BBE70E88E2353 ![file] Figure 7C has a series of lanes that are remarkably similar to a blot formed by duplication of four lanes that has made appearances in three other papers. In each appearance it takes on a new identity. Commented on in: https: pubpeer.com publications 6BF6BCD78CF68B8B1DC710A72C8656 ![file] Figure 7D has actin lanes that look quite like lanes found in three other papers. Usually it hales as  actin , but once took the nom de plume of  AMPK . Commented on in: https: pubpeer.com publications 6BF6BCD78CF68B8B1DC710A72C8656 ![file] ,