Immune synapse formation determines interaction forces between T cells and antigen-presenting cells measured by...

Area of Science:

• Immunology
• Biophysics
• Cellular Biology

Background:

• T cell activation requires recognition of antigens presented by MHC molecules on APCs, forming an immune synapse (IS).
• While IS molecular composition is known, the biophysics and interaction forces remain poorly understood.

Purpose of the Study:

• To measure the interaction forces between T cells and APCs during IS formation using AFM.
• To correlate these forces with the kinetics of synapse formation.
• To investigate the role of LFA-1/ICAM-1 interactions in T cell-APC adhesion.

Main Methods:

• Atomic Force Microscopy (AFM) was used to measure interaction forces between T cells and APCs recognizing specific antigenic peptides.
• High-throughput multispectral imaging flow cytometry quantified synapse formation kinetics.
• The effect of LFA-1 inhibitor BIRT377 on interaction forces was assessed.

Main Results:

• Interaction forces increased from 1-2 nN to a maximum of ~14 nN at 30 minutes, then decreased.
• These force dynamics correlated with IS formation kinetics, peaking at 30 minutes.
• Inhibition of LFA-1 by BIRT377 significantly reduced interaction forces, confirming LFA-1/ICAM-1's importance.

Conclusions:

• Biophysical measurements provide precise values for T cell-APC interaction forces.
• These forces are dynamic, peaking during maximal synapse formation.
• LFA-1/ICAM-1 interactions are critical for robust T cell-APC adhesion.