Robust T cell activation requires an eIF3-driven burst in T cell receptor translation

De Silva, Dasmanthie; Ferguson, Lucas; Chin, Grant H.; Smith, Benjamin E.; Apathy, Ryan A.; Roth, Theodore L.; Blaeschke, Franziska; Kudla, Marek; Marson, Alexander; Ingolia, Nicholas T.; Cate, Jamie HD

doi:10.7554/elife.74272

Title: Robust T cell activation requires an eIF3-driven burst in T cell receptor translation

Journal Article · 31 December 2021 · eLife

DOI: https://doi.org/10.7554/elife.74272 · OSTI ID:2470686

^[1]; Ferguson, Lucas ^[2]; Chin, Grant H. ^[2]; Smith, Benjamin E. ^[2]; Apathy, Ryan A. ^[3]; Roth, Theodore L. ^[3]; Blaeschke, Franziska ^[4]; Kudla, Marek ^[2]; Marson, Alexander ^[5];

^[2];

^[6]

Univ. of California, Berkeley, CA (United States); The J. David Gladstone Institutes, San Francisco, CA (United States)
Univ. of California, Berkeley, CA (United States)
Univ. of California, San Francisco, CA (United States)
Gladstone Institutes, San Francisco, CA (United States). UCSF Institute of Genomic Immunology
Univ. of California, San Francisco, CA (United States); Gladstone Institutes, San Francisco, CA (United States). UCSF Institute of Genomic Immunology; Chan Zuckerberg Biohub, San Francisco, CA (United States); Parker Institute for Cancer Immunotherapy, San Francisco, CA (United States); Univ. of California, Berkeley, CA (United States)
Univ. of California, Berkeley, CA (United States); The J. David Gladstone Institutes, San Francisco, CA (United States); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

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.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: National Institutes of Health (NIH); USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2470686

Journal Information:: eLife, Journal Name: eLife Vol. 10; ISSN 2050-084X

Publisher:: eLife Sciences Publications, Ltd.Copyright Statement

Country of Publication:: United States

Language:: English

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Title: Robust T cell activation requires an eIF3-driven burst in T cell receptor translation

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