Complex and dynamic redistribution of NF-ΚB signaling intermediates in response to T cell receptor stimulation

The central zone of the supramolecular activation cluster (c-SMAC) is a zone of T cell receptor (TCR) enrichment that forms at a T cell/antigen-presenting cell (APC) junction in response to antigen stimulation. We demonstrate that there is a surprisingly complex relocalization process that brings PKCθ and Bcl10, two intermediates in TCR activation of NF-κB, to the cytoplasmic face of the c-SMAC. TCR activation causes enrichment of PKCθ at the c-SMAC, followed by Bcl10 relocalization to punctate cytoplasmic structures, often at sites distant from the c-SMAC. These Bcl10 structures then undergo further relocalization, becoming enriched at the c-SMAC. TCR activation of NF-κB therefore involves the dynamic relocalization of multiple signaling intermediates, with distinct phases proximal to and distant from the c-SMAC.