The immunological synapse controls local and global calcium signals in T lymphocytes

Abstract

Cell polarization is a key feature of T-cell function. The immunological synapse (IS) between T cells and antigen-presenting cells is a beautiful example of how polarization of cells is used to guide cell function. Receptors, signal transducers, the cytoskeleton, and organelles are enriched at or depleted from the IS after its formation, and in many cases these re-localizations have already been linked with certain T-cell functions. One key step for T-cell activation is a rise in the cytoplasmic calcium concentration. Whereas it is undisputed that the IS initiates and controls calcium signals in T cells, very little is known about the role of T-cell polarization for calcium signals and calcium-dependent signal transduction. We briefly summarize the basic commonly agreed principles of IS-dependent calcium signal generation but then focus on the less well understood influence of polarization on calcium signals. The discussion of the role of polarization for calcium signals leads to a model how the IS controls local and global calcium signals and calcium-dependent T-cell functions. We develop a theoretical formalism based on existing spatiotemporal calcium dynamic simulations to better understand the model in the future and allow further predictions which can be tested by fast, high resolution live-cell microscopy.