瑞士意大利大学生物医学研究所Roger Geiger研究组取得最新进展。他们发现了蛋白质翻译维持T细胞准备的动力学。2020年7月6日出版的《自然—免疫学》杂志发表了这项成果。

使用脉冲SILAC方法，他们研究了人类天然和活化T细胞中mRNA翻译动力学和蛋白质更新动力学。他们的数据集发现，维持T细胞静止的转录因子具有结构性高更新率，这促进了它们在激活后的耗竭。此外，未加工的T细胞维持了令人惊讶的大量空转的核糖体以及242种受抑制的mRNA种类和糖酵解酶的储库。这些成分在刺激后迅速参与，促进了立即翻译和糖酵解转换，从而加速了T细胞活化程序。

他们的数据阐明了有关T细胞如何维持准备状态以发起快速免疫反应的新见解，并提供了T细胞中蛋白质更新、绝对翻译动力学和蛋白质合成速率的资源（https://www.immunomics.ch）。Geiger及其同事使用SILAC和质谱技术研究了人类T细胞中的蛋白质更新，并研究了天然T细胞如何保持其静止状态并转变为活化状态细胞。

研究人员表示，为响应病原体威胁，天然T细胞从静止状态快速转变为激活状态，但其潜在机制尚未完全了解。

附：英文原文

Title: Dynamics in protein translation sustaining T cell preparedness

Author: Tobias Wolf, Wenjie Jin, Giada Zoppi, Ian A. Vogel, Murodzhon Akhmedov, Christopher K. E. Bleck, Tim Beltraminelli, Jan C. Rieckmann, Neftali J. Ramirez, Marco Benevento, Samuele Notarbartolo, Dirk Bumann, Felix Meissner, Bodo Grimbacher, Matthias Mann, Antonio Lanzavecchia, Federica Sallusto, Ivo Kwee, Roger Geiger

Issue&Volume: 2020-07-06

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). Geiger and colleagues use SILAC and mass spectrometry to study protein turnover in human T cells and examine how naive T cells maintain their quiescence and transition to activated cells.

DOI: 10.1038/s41590-020-0714-5

Source: https://www.nature.com/articles/s41590-020-0714-5