Exploring How Cytoskeleton Dynamics Tunes T Cell Activation at the Immunological Synapse

During T cell immune responses, actin dynamics facilitates the scanning of antigen-presenting cells (APCs) and the antigen engagement by the T cell receptor (TCR), initiating activation. This activation, in turn, promotes further cytoskeletal rearrangements, leading to the formation of a specialized T cell/APC adhesion structure known as the immunological synapse (IS). Actin and tubulin dynamics at the IS sustain activating signals by generating forces that activate signaling molecules and integrins while polarizing the centrosome and the endosomal compartment toward the IS center. The polarized endosomal compartment delivers signaling molecules and activating receptors to the activation site, along with secretory vesicles, during the effector phase. Thus, the IS is essential for full T cell activation and effector function. Regulation of cytoskeleton rearrangements relies on a network of signaling molecules and cytoskeleton-regulatory proteins tightly controlled in space and time. In this review, we examine the roles of key regulators, such as SSH1 phosphatase and LIMK1, in actin and tubulin dynamics and discuss the relevance of mechanotransduction in T cell activation.