Robust T cell activation requires an eIF3-driven burst in T cell receptor translation.
Robust T cell activation requires an eIF3-driven burst in T cell receptor translation.
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DOI：
10.7554/elife.74272
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发表时间：
2021-12-31
期刊：
影响因子：
7.7
通讯作者：
Cate JH
中科院分区：
文献类型：
--
作者：
De Silva D;Ferguson L;Chin GH;Smith BE;Apathy RA;Roth TL;Blaeschke F;Kudla M;Marson A;Ingolia NT;Cate JH
T细胞的激活需要细胞蛋白质合成的快速激增。然而，翻译起始在特定基因的早期诱导中的作用仍不清楚。在这里，我们展示了人翻译起始因子eIF 3与选择的免疫系统相关mRNA相互作用，包括编码T细胞受体（TCR）亚基TCRA和TCRB的mRNA。eIF 3与TCRA和TCRB mRNA 3 '-非翻译区（3'-UTR）的结合依赖于CD 28辅助受体信号传导，并调节稳健T细胞活化所需的TCR翻译爆发。使用TCRA或TCRB 3 '-UTR来控制抗CD 19嵌合抗原受体（CAR）的表达提高了CAR-T细胞体外杀死肿瘤细胞的能力。这些结果确定了eIF 3介导的翻译控制的新机制，可以帮助T细胞工程免疫治疗应用。
Activation of T cells requires a rapid surge in cellular protein synthesis. However, the role of translation initiation in the early induction of specific genes remains unclear. Here, we show human translation initiation factor eIF3 interacts with select immune system related mRNAs including those encoding the T cell receptor (TCR) subunits TCRA and TCRB. Binding of eIF3 to the TCRA and TCRB mRNA 3’-untranslated regions (3’-UTRs) depends on CD28 coreceptor signaling and regulates a burst in TCR translation required for robust T cell activation. Use of the TCRA or TCRB 3’-UTRs to control expression of an anti-CD19 chimeric antigen receptor (CAR) improves the ability of CAR-T cells to kill tumor cells in vitro. These results identify a new mechanism of eIF3-mediated translation control that can aid T cell engineering for immunotherapy applications.