Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, United States; The J. David Gladstone Institutes, San Francisco, United States
Lucas Ferguson
Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, United States
Grant H Chin
Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, United States
Benjamin E Smith
School of Optometry, University of California, Berkeley, Berkeley, United States
Ryan A Apathy
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States
Theodore L Roth
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States
Franziska Blaeschke
Gladstone-UCSF Institute of Genomic Immunology, San Francisco, United States
Marek Kudla
Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, United States
Alexander Marson
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States; Gladstone-UCSF Institute of Genomic Immunology, San Francisco, United States; Diabetes Center, University of California, San Francisco, San Francisco, United States; Chan Zuckerberg Biohub, San Francisco, United States; Department of Medicine, University of California, San Francisco, San Francisco, United States; Parker Institute for Cancer Immunotherapy, San Francisco, United States; Innovative Genomics Institute, University of California, Berkeley, Berkeley, United States
Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, United States; California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, United States
Department of Molecular and Cell Biology, University of California-Berkeley, Berkeley, United States; The J. David Gladstone Institutes, San Francisco, United States; Innovative Genomics Institute, University of California, Berkeley, Berkeley, United States; California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, United States; Department of Chemistry, University of California-Berkeley, Berkeley, United States; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, 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.
