T Cell Activation through Isolated Tight Contacts.

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• T cells interact with antigen-presenting cells (APCs) through dynamic cell protrusions to find antigens.
• The precise spatiotemporal events governing T cell receptor (TCR) triggering and signal amplification during initial contact formation remain unclear.
• Understanding these early events is crucial for deciphering T cell activation.

Purpose of the Study:

• To resolve T cell receptor (TCR)-dependent signaling dynamics at early and tight cell-cell contacts.
• To elucidate the molecular mechanisms underlying T cell activation during synapse formation.
• To investigate the roles of CD45, cortical actin, and LFA in T cell contacts.

Main Methods:

• Combined interference-reflectance microscopy (IRM) and single-molecule localization microscopy (SMLM) in live cells.
• Live-cell imaging to visualize TCR signaling events at the T cell-APC interface.
• High-resolution microscopy to track molecular recruitment and segregation.

Main Results:

• Early T cell contacts are sufficient for robust TCR triggering and ZAP-70 recruitment.
• TCR activation and ZAP-70 recruitment increase and redistribute to contact edges with cell spreading.
• CD45 segregates from TCR at tight contacts and localizes to membrane regions with high curvature.
• Cortical actin and LFA were observed in contact regions of intermediate tightness.

Conclusions:

• Early T cell contacts play a critical role in initiating T cell activation.
• T cell contacts are dynamic entities involved in both antigen sensing and immune decision-making.
• The findings provide molecular-level insights into the progression of T cell-APC interactions.