Abstract

There is emerging evidence that exocytosis plays an important role in regulating T cell receptor (TCR) signaling. The trafficking molecules involved in lytic granule (LG) secretion in cytotoxic T lymphocytes (CTL) have been well-studied due to the immune disorder known as familial hemophagocytic lymphohistiocytosis (FHLH). However, the knowledge of trafficking machineries regulating the exocytosis of receptors and signaling molecules remains quite limited. In this review, we summarize the reported trafficking molecules involved in the transport of the TCR and downstream signaling molecules to the cell surface. By combining this information with the known knowledge of LG exocytosis and general exocytic trafficking machinery, we attempt to draw a more complete picture of how the TCR signaling network and exocytic trafficking matrix are interconnected to facilitate T cell activation. This also highlights how membrane compartmentalization facilitates the spatiotemporal organization of cellular responses that are essential for immune functions.

Highlights

  • The key signaling molecules involved in the T Cell Receptor (TCR) signaling network have been well-characterized

  • Extensive research has focused on understanding the TCR signaling network and signal-regulating mechanisms during T cell activation due to the essential roles of T cells in the adaptive immune system

  • We attempted to summarize the known trafficking machinery involved in the exocytosis of TCR, downstream signaling molecules and effectors during TCR activation

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Summary

New Insights into How Trafficking Regulates T Cell Receptor Signaling

Jieqiong Lou 1, 2, Jérémie Rossy 1, 2, Qiji Deng 1, 2, Sophie V. We summarize the reported trafficking molecules involved in the transport of the TCR and downstream signaling molecules to the cell surface By combining this information with the known knowledge of LG exocytosis and general exocytic trafficking machinery, we attempt to draw a more complete picture of how the TCR signaling network and exocytic trafficking matrix are interconnected to facilitate T cell activation. This highlights how membrane compartmentalization facilitates the spatiotemporal organization of cellular responses that are essential for immune functions

INTRODUCTION
TCR Signaling and Trafficking
EXOCYTOSIS MACHINERY OF EFFECTOR AND SIGNALING MOLECULES
Oculocerebrorenal syndrome of Lowe OCRL
Proposed functions
High Medium Low High Low Low Medium Low
ADDITIONAL TRAFFICKING MECHANISMS FOR TCR SIGNALING MOLECULES
CONCLUSION

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