Abstract

The cell’s ability to communicate with the extracellular environment, with other cells, and with itself is a crucial feature of eukaryotic organisms. In the immune system, T lymphocytes assemble a specialized structure upon contact with antigen-presenting cells bearing a peptide-major histocompatibility complex ligand, known as the immunological synapse (IS). The IS has been extensively characterized as a signaling platform essential for T-cell activation. Moreover, emerging evidence identifies the IS as a device for vesicular traffic-mediated cell-to-cell communication as well as an active release site of soluble molecules. Here, we will review recent advances in the role of vesicular trafficking in IS assembly and focused secretion of microvesicles at the synaptic area in naïve T cells and discuss the role of the IS in transcellular communication.

Highlights

  • T-cell activation crucially depends on the assembly of a complex supramolecular structure, known as the immunological synapse (IS), at the T-cell interface with the antigen-presenting cell (APC)[1]

  • The synaptic cleft has been reported as a site for trogocytosis, a process exploited by T cells to extract peptide ligand associated with major histocompatibility complex (pMHC) from the APC during the endocytosis of engaged T-cell antigen receptor (TCR), which thereby can sustain signaling at endosomes[6,7,8,9,10,11,12]

  • The IS is a very dynamic structure that must be finely regulated in time and space to induce a productive immune response

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Summary

Introduction

T-cell activation crucially depends on the assembly of a complex supramolecular structure, known as the immunological synapse (IS), at the T-cell interface with the antigen-presenting cell (APC)[1]. Several vesicle-soluble N-ethylmaleimide-sensitive factor attachment protein receptors (v-SNAREs) and target-SNAREs (t-SNAREs) are recruited to the IS and are implicated in TCR (VAMP327,33, syntaxin[433], and SNAP2333) and LAT (VAMP734) targeting to the synaptic membrane These data indicate that intracellular vesicular trafficking is essential for modulating both the intensity and duration of signaling at the IS through the polarized transport of specific molecules to the synaptic cleft. Extracellular traffic at the immunological synapse Emerging evidence indicates that the IS is a site of intense intracellular trafficking and an area of extracellular vesicle release Based on these observations, it has been proposed that the cSMAC can be divided into two components: the endocSMAC, a membrane domain where TCR signaling occurs, and the exo-cSMAC, an extracellular region between the T cell and the APC, which is characterized by the presence of TCR-enriched extracellular vesicles[35]. Extracellular vesicles released by APCs mediate a counter-strategy to protect recipient T cells from HIV-1 by delivering apolipoprotein B editing complex 3G, a key suppressor of HIV-1 replication[71,72]

Conclusions
17. Springer TA
35. Dustin ML
39. Edgar JR
PubMed Abstract
Findings
57. Soares H: HIV-1 Intersection with CD4 T Cell Vesicle Exocytosis
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