The immunological synapse: a cause or consequence of T-cell receptor triggering?

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• The immunological synapse (IS) is crucial for T cell activation, initially described as a three-ring structure.
• The central supramolecular activation cluster (cSMAC) was thought to sustain T-cell receptor (TCR) signaling.
• This typical structure is not always observed, particularly with dendritic cells.

Purpose of the Study:

• To review the historical understanding of the cSMAC's role in T cell activation.
• To present new data on the function of the cSMAC.
• To investigate the role of the cSMAC in TCR internalization.

Main Methods:

• Literature review of IS formation and function.
• Analysis of T cell-APC interactions.
• Microscopy and imaging techniques to observe TCR dynamics.

Main Results:

• TCR signaling occurs in microclusters and diminishes as TCRs approach the cSMAC.
• The cSMAC may not be required for initial T cell activation or sustained signaling.
• Recent data indicate the cSMAC facilitates the internalization of exhausted TCRs through phagocytosis.

Conclusions:

• The role of the cSMAC in T cell activation is re-evaluated, moving beyond sustained signaling.
• The cSMAC appears to be involved in TCR down-regulation and removal.
• Phagocytosis of exhausted TCRs by the cSMAC is a newly identified function.