A calcium-dependent PKC, independent of NF-κB, is required for proper initiation of chromatin decondensation during T-cell activation.

Abstract

Abstract Following antigen engagement at the T-cell receptor (TCR), there are two known signaling pathways that are involved in the activation of T-cells, initiated by DAG and IP3. These signaling pathways ultimately lead to chromatin decondensation, which is required for subsequent T-cell proliferation mediated by IL-2. It has previously been demonstrated that intracellular calcium is necessary for proper chromatin decondensation but that calcium does not act through transcription factor NFAT. In this study, we demonstrate that PKC, activated through DAG, is also required for proper chromatin decondensation. Furthermore, we show that calcium is required for PKC mediated chromatin decondensation, suggesting that a calcium dependent isoform of PKC is involved in the process. Interestingly, PKC but not IP3 is required for subsequent competence of T-cells to respond to IL-2 signaling. Finally, we show that PKC does not act downstream through NF-κB to decondense chromatin and our data suggest that NF-κB is not required for IL-2 competence. Collectively, these data could be suggestive of multiple mechanisms to control the activation and proliferation of T-cells during an immune response.