Araki Koichi, Morita Masahiro, Bederman Annelise G, Konieczny Bogumila T, Kissick Haydn T, Sonenberg Nahum, Ahmed Rafi
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA.
Department of Biochemistry, McGill University, Montreal, Canada.
Nat Immunol. 2017 Sep;18(9):1046-1057. doi: 10.1038/ni.3795. Epub 2017 Jul 17.
Translation is a critical process in protein synthesis, but translational regulation in antigen-specific T cells in vivo has not been well defined. Here we have characterized the translatome of virus-specific CD8 effector T cells (T cells) during acute infection of mice with lymphocytic choriomeningitis virus (LCMV). Antigen-specific T cells exerted dynamic translational control of gene expression that correlated with cell proliferation and stimulation via the T cell antigen receptor (TCR). The translation of mRNAs that encode translation machinery, including ribosomal proteins, was upregulated during the T cell clonal-expansion phase, followed by inhibition of the translation of those transcripts when the CD8 T cells stopped dividing just before the contraction phase. That translational suppression was more pronounced in terminal effector cells than in memory precursor cells and was regulated by antigenic stimulation and signals from the kinase mTOR. Our studies show that translation of transcripts encoding ribosomal proteins is regulated during the differentiation of CD8 T cells and might have a role in fate 'decisions' involved in the formation of memory cells.
翻译是蛋白质合成中的一个关键过程,但体内抗原特异性T细胞的翻译调控尚未得到很好的界定。在此,我们对小鼠感染淋巴细胞性脉络丛脑膜炎病毒(LCMV)急性感染期间病毒特异性CD8效应T细胞(T细胞)的翻译组进行了表征。抗原特异性T细胞对基因表达进行动态翻译控制,这与通过T细胞抗原受体(TCR)的细胞增殖和刺激相关。在T细胞克隆扩增阶段,编码翻译机器(包括核糖体蛋白)的mRNA的翻译上调,随后当CD8 T细胞在收缩期前停止分裂时,这些转录本的翻译受到抑制。这种翻译抑制在终末效应细胞中比在记忆前体细胞中更明显,并且受抗原刺激和激酶mTOR发出的信号调节。我们的研究表明,编码核糖体蛋白的转录本的翻译在CD8 T细胞分化过程中受到调控,并且可能在记忆细胞形成所涉及的命运“决定”中发挥作用。