Mechanosurveillance: Tiptoeing T Cells.

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• T cell recognition of antigens is crucial for adaptive immunity.
• T cells must detect rare peptide/MHC complexes amidst numerous non-stimulatory ones on cell surfaces.
• The glycocalyx on target cells presents a physical barrier to T cell antigen recognition.

Purpose of the Study:

• To review how T cell microvilli and target cell glycocalyx properties influence T cell activation.
• To integrate biophysical forces and molecular dynamics into understanding T cell antigen recognition.

Main Methods:

• Review of studies on T cell plasma membrane ultrastructure.
• Assessment of biophysical aspects including mechanical forces and molecular signaling.
• Analysis of T cell microvilli plasticity and glycocalyx physicochemical properties.

Main Results:

• T cell microvilli actively penetrate the glycocalyx barrier, facilitating T cell receptor (TCR) engagement with peptide/MHC (pMHC) complexes.
• The physical properties of the glycocalyx and T cell microvilli impact the efficiency of antigen detection.
• Mechanical forces exerted by TCRs and the distribution/mobility of signaling molecules are key to T cell activation.

Conclusions:

• T cell microvilli plasticity and glycocalyx characteristics are critical determinants of early T cell activation events.
• A comprehensive view integrating ultrastructure, biophysics, and molecular signaling is needed for understanding T cell antigen recognition.