Dynamics of T cell activation mediated by eIF3 interactions with T cell receptor mRNAs

Activation of T cells requires a global surge in cellular protein synthesis, which is accompanied by a large increase in translation initiation. A central component of the translation initiation machinery–the multi-subunit eukaryotic initiation factor 3 (eIF3)–is rapidly turned on when quiescent T cells are stimulated. However, the precise role eIF3 plays in activated T cells is not known. Using a global transcriptome cross-linking approach, we show that human eIF3 interacts with a distinct set of mRNAs in activated Jurkat cells. A subset of these mRNAs, including those encoding the T cell receptor (TCR) subunits TCRA and TCRB, crosslink to eIF3 across the entire length of the mRNA. Fluorescence in situ hybridization studies reveal both and mRNAs form granules, potentially acting as translation “hot-spots.” We further find that elements in the 3’-untranslated regions (3’-UTRs) of the and mRNAs that directly interact with eIF3 control the early dynamics of TCR translation in a CD28-dependent manner, as well as the extent of T cell activation. These results highlight a new role for eIF3 in regulation of translation dynamics and provide insights that can guide engineering of T cells for cell immunotherapy applications.