TCR-pMHC kinetics under force in a cell-free system show no intrinsic catch bond, but a minimal encounter duration...

Area of Science:

• Immunology
• Biophysics
• Molecular Biology

Background:

• T cell activation relies on T cell receptor (TCR)-peptide-MHC (pMHC) interactions.
• Catch bonds, a type of molecular interaction, have been suggested to characterize activating TCR-pMHC interactions.

Purpose of the Study:

• To investigate whether catch bond formation is an intrinsic feature of the TCR-pMHC interaction.
• To determine the relationship between TCR-pMHC dissociation kinetics and T cell activation potency.

Main Methods:

• Utilized a laminar flow chamber to measure 2D TCR-pMHC dissociation and association kinetics in a cell-free system.
• Analyzed interactions within the 6- to 15-pN force range, previously linked to catch-slip transitions.

Main Results:

• No catch bonds were observed during TCR-pMHC dissociation.
• The measured off-rate correlated significantly with peptide activation potency.
• Association kinetics were better described by a minimal encounter duration model, not a standard on-rate constant.

Conclusions:

• Catch bond formation is not an intrinsic characteristic of the TCR-pMHC molecular bond.
• Membrane fluidity and dynamics likely play a significant role in TCR-pMHC bond formation during T cell activation.