The chaperonin CCT controls T cell receptor-driven 3D configuration of centrioles.

T lymphocyte activation requires the formation of immune synapses (IS) with antigen-presenting cells. The dynamics of membrane receptors, signaling scaffolds, microfilaments, and microtubules at the IS determine the potency of T cell activation and subsequent immune response. Here, we show that the cytosolic chaperonin CCT (chaperonin-containing TCP1) controls the changes in reciprocal orientation of the centrioles and polarization of the tubulin dynamics induced by T cell receptor in T lymphocytes forming an IS. CCT also controls the mitochondrial ultrastructure and the metabolic status of T cells, regulating the de novo synthesis of tubulin as well as posttranslational modifications (poly-glutamylation, acetylation, Δ1 and Δ2) of αß-tubulin heterodimers, fine-tuning tubulin dynamics. These changes ultimately determine the function and organization of the centrioles, as shown by three-dimensional reconstruction of resting and stimulated primary T cells using cryo-soft x-ray tomography. Through this mechanism, CCT governs T cell activation and polarity.

Mechanisms of polarized cell-cell communication of T lymphocytes.

Cell-cell communication comprises a variety of molecular mechanisms that immune cells use to respond appropriately to diverse pathogenic stimuli. T lymphocytes polarize in response to different stimuli, such as cytokines, adhesion to specific ligands and cognate antigens presented in the context of MHC. Polarization takes different shapes, from migratory front-back polarization to the formation of immune synapses (IS). The formation of IS between a T cell and an antigen-presenting cell involves early events of receptor-ligand interaction leading to the reorganization of the plasma membrane and the cytoskeleton to orchestrate vesicular and endosomal traffic and directed secretion of several types of mediators, including cytokines and nanovesicles. Cell polarization involves the repositioning of many subcellular organelles, including the endosomal compartment, which becomes an effective platform for the shuttling of molecules as vesicular cargoes that lately will be secreted to transfer information to antigen-presenting cells. Overall, the polarized interaction between a T cell and APC modifies the recipient cell in different ways that are likely lineage-dependent, e.g. dendritic cells, B cells or even other T cells. In this review, we will discuss the mechanisms that mediate the polarization of different membrane receptors, cytoskeletal components and organelles in T cells in a variety of immune contexts.