Hierarchy of signaling thresholds downstream of the T cell receptor and the Tec kinase ITK

Significance In order to help fight off pathogens and malignancies, CD8 + T lymphocytes send signals from the T cell receptor (TCR) through multiple transcription factor pathways. The strength of the TCR signal is modulated in part by the Tec kinase ITK, whose activity helps create graded amounts of T cell activation genes. We report that some signaling pathways rely more heavily on ITK support for robust activation. During suboptimal signaling conditions, we measured the reduced amount of NF-κB activation and early gene induction within digital NFAT- and Erk1/2-activated cells. Our work highlights the importance of signal strength in activating T cells and uncovers details about the supplemental role of ITK in proximal TCR signaling.