PMID- 34970966
OWN - NLM
STAT- MEDLINE
DCOM- 20220121
LR  - 20240405
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 10
DP  - 2021 Dec 31
TI  - Robust T cell activation requires an eIF3-driven burst in T cell receptor 
      translation.
LID - 10.7554/eLife.74272 [doi]
LID - e74272
AB  - 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.
CI  - (c) 2021, De Silva et al.
FAU - De Silva, Dasmanthie
AU  - De Silva D
AUID- ORCID: 0000-0001-6824-0850
AD  - Department of Molecular and Cell Biology, University of California-Berkeley, 
      Berkeley, United States.
AD  - The J. David Gladstone Institutes, San Francisco, United States.
FAU - Ferguson, Lucas
AU  - Ferguson L
AD  - Department of Molecular and Cell Biology, University of California-Berkeley, 
      Berkeley, United States.
FAU - Chin, Grant H
AU  - Chin GH
AD  - Department of Molecular and Cell Biology, University of California-Berkeley, 
      Berkeley, United States.
FAU - Smith, Benjamin E
AU  - Smith BE
AD  - School of Optometry, University of California, Berkeley, Berkeley, United States.
FAU - Apathy, Ryan A
AU  - Apathy RA
AD  - Department of Microbiology and Immunology, University of California, San 
      Francisco, San Francisco, United States.
FAU - Roth, Theodore L
AU  - Roth TL
AD  - Department of Microbiology and Immunology, University of California, San 
      Francisco, San Francisco, United States.
FAU - Blaeschke, Franziska
AU  - Blaeschke F
AD  - Gladstone-UCSF Institute of Genomic Immunology, San Francisco, United States.
FAU - Kudla, Marek
AU  - Kudla M
AD  - Department of Molecular and Cell Biology, University of California-Berkeley, 
      Berkeley, United States.
FAU - Marson, Alexander
AU  - Marson A
AD  - Department of Microbiology and Immunology, University of California, San 
      Francisco, San Francisco, United States.
AD  - Gladstone-UCSF Institute of Genomic Immunology, San Francisco, United States.
AD  - Diabetes Center, University of California, San Francisco, San Francisco, United 
      States.
AD  - Chan Zuckerberg Biohub, San Francisco, United States.
AD  - Department of Medicine, University of California, San Francisco, San Francisco, 
      United States.
AD  - Parker Institute for Cancer Immunotherapy, San Francisco, United States.
AD  - Innovative Genomics Institute, University of California, Berkeley, Berkeley, 
      United States.
FAU - Ingolia, Nicholas T
AU  - Ingolia NT
AUID- ORCID: 0000-0002-3395-1545
AD  - Department of Molecular and Cell Biology, University of California-Berkeley, 
      Berkeley, United States.
AD  - California Institute for Quantitative Biosciences, University of California, 
      Berkeley, Berkeley, United States.
FAU - Cate, Jamie Hd
AU  - Cate JH
AUID- ORCID: 0000-0001-5965-7902
AD  - Department of Molecular and Cell Biology, University of California-Berkeley, 
      Berkeley, United States.
AD  - The J. David Gladstone Institutes, San Francisco, United States.
AD  - Innovative Genomics Institute, University of California, Berkeley, Berkeley, 
      United States.
AD  - California Institute for Quantitative Biosciences, University of California, 
      Berkeley, Berkeley, United States.
AD  - Department of Chemistry, University of California-Berkeley, Berkeley, United 
      States.
AD  - Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley 
      National Laboratory, Berkeley, United States.
LA  - eng
SI  - GEO/GSE191306
GR  - R01 GM065050/GM/NIGMS NIH HHS/United States
GR  - DP2 CA195768/NH/NIH HHS/United States
GR  - P30EY003176/NH/NIH HHS/United States
GR  - S10 OD018174/OD/NIH HHS/United States
GR  - DP2 CA195768/CA/NCI NIH HHS/United States
GR  - R01-GM065050/NH/NIH HHS/United States
GR  - P30 EY003176/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20211231
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 0 (Eukaryotic Initiation Factor-3)
RN  - 0 (Receptors, Antigen, T-Cell)
SB  - IM
MH  - Cell Line
MH  - Eukaryotic Initiation Factor-3/*genetics/metabolism
MH  - Humans
MH  - Lymphocyte Activation/*genetics
MH  - Receptors, Antigen, T-Cell/*immunology
MH  - T-Lymphocytes/*immunology
PMC - PMC8758144
OTO - NOTNLM
OT  - CD28
OT  - T cell receptor
OT  - cell biology
OT  - cellular immunotherapy
OT  - chimeric antigen receptor
OT  - eIF3
OT  - human
OT  - immunology
OT  - inflammation
OT  - protein synthesis
COIS- DD, JC A provisional patent application has been filed on some of the work 
      presented herein, LF, GC, BS, RA, FB, MK, NI No competing interests declared, TR 
      is a co-founder of Arsenal Therapeutics, AM is a compensated co-founder, member 
      of the boards of directors, and a member of the scientific advisory boards of 
      Spotlight Therapeutics and Arsenal Biosciences. Was a compensated member of the 
      scientific advisory board at PACT Pharma and was a compensated advisor to Juno 
      Therapeutics. Owns stock in Arsenal Biosciences, Spotlight Therapeutics, PACT 
      Pharma and Merck. AM has received fees from Vertex, Merck, Amgen, Trizell, 
      Genentech, AlphaSights, Rupert Case Management and Bernstein. Is an investor in 
      and informal advisor to Offline Ventures. The Marson lab has received research 
      support from Juno Therapeutics, Epinomics, Sanofi, GlaxoSmithKline, Gilead, and 
      Anthem
EDAT- 2022/01/01 06:00
MHDA- 2022/01/22 06:00
PMCR- 2021/12/31
CRDT- 2021/12/31 08:37
PHST- 2021/09/28 00:00 [received]
PHST- 2021/12/30 00:00 [accepted]
PHST- 2022/01/01 06:00 [pubmed]
PHST- 2022/01/22 06:00 [medline]
PHST- 2021/12/31 08:37 [entrez]
PHST- 2021/12/31 00:00 [pmc-release]
AID - 74272 [pii]
AID - 10.7554/eLife.74272 [doi]
PST - epublish
SO  - Elife. 2021 Dec 31;10:e74272. doi: 10.7554/eLife.74272.