Functional Anatomy of T Cell Activation and Synapse Formation

Abstract

T cell activation and function require a structured engagement of antigen-presenting cells. These cell contacts are characterized by two distinct dynamics in vivo: transient contacts resulting from promigratory junctions called immunological kinapses or prolonged contacts from stable junctions called immunological synapses. Kinapses operate in the steady state to allow referencing to selfpeptide-MHC (pMHC) and searching for pathogen-derived pMHC. Synapses are induced by T cell receptor (TCR) interactions with agonist pMHC under specific conditions and correlate with robust immune responses that generate effector and memory T cells. High-resolution imaging has revealed that the synapse is highly coordinated, integrating cell adhesion, TCR recognition of pMHC complexes, and an array of activating and inhibitory ligands to promote or prevent T cell signaling. In this review, we examine the molecular components, geometry, and timing underlying kinapses and synapses. We integrate recent molecular and physiological data to provide a synthesis and suggest ways forward.

Cell-Cell Communication Via Extracellular Membrane Vesicles and Its Role in the Immune Response

“…The set of receptors and ligands making contact with each other in cells determine the phenotypic changes in those cells during or after the contact. In addition, direct cell-cell contact may allow the directional release of intracellular molecules from a donor cell only to a recipient (target) cell at the interface of the contact (Fooksman et al, 2010). This type of molecule release may minimize unwanted bystander effects of the immune effector molecules on cells in close proximity of the target cell.…”

SCIMP, a Transmembrane Adaptor Protein Involved in Major Histocompatibility Complex Class II Signaling

“…This leads to the formation of the immunological synapse (IS) at the cell-cell contact site. The hallmark of the IS is accumulation of T cell receptors (TCRs) paired with peptide-MHC, together with pairs of adhesion and costimulatory molecules (14).…”

A role for novel lipid interactions in the dynamic recruitment of SNX27 to the T-cell immune synapse

“…[19][20][21][22] Lipid composition is also altered to allow the signaling, adhesion, and membrane trafficking adjustments needed for conversion to an activated state. 23,24 The IS thus presents a unique and powerful model for studying the role and dynamics of different molecules in activation-induced polarized recycling. 25 SNX27 displays PX-dependent endosomal localization that was positive for early endosomes (EE) and ERC in resting T lymphocytes.…”