cinetica di associazione e dissociazione del legame TCR-pMHC sotto forza in un sistema privo di cellule

The association of the T-Cell Receptor (TCR) to peptide bound to major histocompatibility complex (pMHC) is the only specific and divisive step which leads to the activation of T-lymphocytes. Even though the intracellular signaling pathways are somewhat well understood, the exact mechanism underlying the recognition of the specific pMHC by its TCR remains unclear. This bond takes place between two membrane bound molecules in 2D that get subjected to disruptive forces. Hence, in order to discern the binding kinetics of TCR-pMHC interaction, measurements of association and dissociation kinetics of the bond under force were done using an automated home-made device, called the Laminar Flow Chamber (LFC) with a strict criteria for single bond molecular conditions. Our experiments were done using 6 different pMHC molecules that bind to three different TCR systems: A6, 1G4 and 0T-1. Our results showcase that catch bonds are not an intrinsic characteristic of the TCR-pMHC interactions, and hence are not necessary for T-cell activation. We also shed light regarding the peculiarity of the OT-1 system and the heterogenous sensitivity of bond formation to forces.