The Immunological Synapse, TCR Microclusters, and T Cell Activation

Abstract

T cell activation begins with the interaction between an antigen-specific T cell and an antigen-presenting cell (APC). This interaction results in the formation of the immunological synapse, which had been considered to be responsible for antigen recognition and T cell activation. Recent advances in imaging analysis have provided new insights into T cell activation. The T cell receptor (TCR) microclusters, TCRs, kinases, and adaptors are generated upon antigen recognition at the interfaces between the T cells and the APCs and serve as a fundamental signaling unit for T cell activation. CD28-mediated costimulation is also found to be regulated by the formation of microclusters. Therefore, the dynamic regulations of TCR and CD28 microcluster formation, migration, and interaction are the key events for the initiation of T cell-mediated immune responses. Comprehensive analyses of the composition and characteristics of the TCR microcluster have identified its dynamic features. This review will outline new discoveries of the microclusters and its related concept in T cell activation.

Mitochondrial-associated endoplasmic reticulum membranes (MAM) form innate immune synapses and are targeted by hepatitis C virus

“…This organization is analogous to the immunologic synapse that forms between a T cell and an antigenpresenting cell in which adhesion molecules tether opposing plasma membranes to establish T-cell receptor signaling microdomains supplied with key signaling factors through membrane interactions (34). Taken together with the role of the MAM in NLRP3 inflammasome signaling (16), our findings indicate that the MAM plays a central role in initiating both the innate immune and inflammatory responses to infection.…”

Tetraspanins CD9 and CD151 at the immune synapse support T‐cell integrin signaling

“…This process is characterized by the formation of a dynamic structure called the immune synapse (IS) at the contact between T cells and APCs [1]. At the T cell side of the IS, T-cell receptors (TCRs) and Correspondence: Dr.Francisco Sánchez-Madrid e-mail: fsmadrid@salud.madrid.org associated molecules accumulate in the central area (central supramolecular activation cluster; cSMAC), while adhesion receptors and integrins reorganize in a surrounding external ring called peripheral SMAC (pSMAC) [1]. The increased IS stability enhances T-cell sensitivity, stimulates cytoskeletal processes, induces downstream signaling, and drives effective T-cell differentiation [2,3].…”

Protein Kinase C-θ Clustering at Immunological Synapses Amplifies Effector Responses in NK Cells

“…A number of distinct lymphocyte activating receptors are known to form microclusters in response to ligand binding (16)(17)(18)(19). It is generally thought that this clustering facilitates signal transduction by providing activating receptors and receptor proximal enzymes privileged access to their substrates and binding partners while at the same time excluding negative regulators.…”