Hierarchy of signaling thresholds downstream of the T cell receptor and the Tec kinase ITK
Michael P. Gallagher, James Conley, Pranitha Vangala, Manuel Garber, Andrea Reboldi, Leslie J. Berg
Abstract
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.