Mesoscale Organization and Dynamics of T Cell Activation Proteins

Careful regulation of T cell activation is important to ensure that signals persist over controlled periods of time. If signals are too short then the immune system will not properly respond, but if signals persist for too long it could result in autoimmune diseases such as Lupus and Type 1 Diabetes. In this work we explore how the spatial structure, organization, and dynamics of a protein complex called the POLKADOTS signalosome allow it to serve as both a positive and negative regulator of the activation signal. Analysis of super-resolution images suggests that proper function of the signalosome involves intricate dynamics of spatial structures: self-assembly of the structural protein Bcl10 into a filamentous, rod-like shape; transport of Malt1, a protease that binds to and decorates the Bcl10 filaments; and autophagic degradation of the signalosome structure from the filament ends. We have incorporated these findings into a simple model of self-assembly and degradation to shed light on the underlying dynamic processes that guide signalosome formation, organization, and degradation.