Force and affinity in ligand discrimination by the TCR

• Recent studies have examined how the TCR–pMHC interaction responds to force.
• The TCR uses a catch bond that responds to specific force thresholds.
• This mechanism may enable discrimination of specific antigens.
• Other interactions in the immunological synapse may impact upon TCR catch-bond formation.

T cell recognition of antigen is a physical process that requires formation of a cell–cell junction that is rich in active force generation. Recently a biomolecular force probe was used to examine how the T cell receptor (TCR)–pMHC interaction responds to force and the consequences of force-dependent interactions for T cell activation. While adhesion and costimulatory molecules in the immunological synapse impact upon the overall force of the interaction, these results suggest that the TCR uses a force-dependent bond – a catch bond – and that it may therefore be important to consider the TCR–pMHC interaction in isolation in the early phases of the decision process. We discuss here these findings in the context of other work on the impact of forces on the TCR and the quantification of interaction in interfaces.