Calcium-dependent PKC is required for chromatin decondensation during the activation of peripheral T cells (IRM6P.651)

Abstract

Abstract Activation of the T cell receptor (TCR) through antigen binding results in chromatin decondensation required for the clonotypic proliferation observed during a proper immune response. Activation of the TCR results in the cleavage of phospholipase biphosphate (PIP2) into diacylglyercol (DAG) and inositol trisphosphate (IP3) by phospholipase C-γ (PLC-γ). Previous studies have shown that both the DAG and IP3 pathways can decondense chromatin, and that intracellular calcium is required for proper TCR-mediated chromatin decondensation. In this study, we used flow cytometry to analyze histone accessibility of chromatin in T cells and found that PKC activation is also required for proper activation-induced chromatin decondensation. Furthermore, we show that calcium is required for proper PKC-mediated chromatin decondensation. Our studies suggest that the PKC isoform(s) required for decondensation may be calcium-dependent. Finally, we show that activation of PKC and not IP3 is required for T cells to gain competence to respond to cytokine stimulation. Taken together, our data suggest that IP3 and PKC signaling work cooperatively to decondense chromatin and regulate clonotypic expansion of T cells during an immune response.