Role of p38 MAPK and NF-κB signaling in chromatin decondensation and acquisition of cytokine competence during T cell activation

Abstract

Abstract A proper immune response is hallmarked by the activation and clonal proliferation of antigen specific T cells. Antigen presentation to the T cell receptor (TCR) leads to the production of two signaling molecules, IP3 and DAG. While IP3 induces calcium flux, DAG activates Protein Kinase C (PKC). The activation of these pathways results in the decondensation of chromatin and the production of interleukin-2 (IL-2), both of which are required for the clonal proliferation of activated T cells. Previous work in our lab demonstrated that the IP3 pathway is sufficient for chromatin decondensation. In this study, we show that this pathway is not sufficient to make cells respond to IL-2. Furthermore, we investigate the role of the DAG pathway, specifically the role of the downstream molecules p38 MAPK and NF-κB, in the decondensation of chromatin and the competence to respond to IL-2 signaling. We found that neither of these molecules play a role in chromatin decondensation and that NF-κB may play a role in IL-2 competence. Collectively, these data, along with our previous findings, suggest that chromatin decondensation and competence to respond to IL-2 may be controlled by IP3 and DAG signaling respectively.