Robust T cell activation requires an eIF3-driven burst in T cell receptor translation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34970966.
- Also identified by DOI 10.7554/eLife.74272 and PMC identifier 8758144.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 <i>TCRA</i> and <i>TCRB</i> 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 <i>TCRA</i> or <i>TCRB</i> 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.
Medical subject headings
- Eukaryotic Initiation Factor-3
- Lymphocyte Activation
- Receptors, Antigen, T-Cell
- T-Lymphocytes