Dynamics of surface receptor interactions required for an immune response

Abstract

We have applied a new method for measuring two dimensional kinetic rates to the study the interactions between receptor important for the regulation of the immune response. The interaction of Cluster of Differentiation (CD) 28 with CD80 stimulates T cell activation, while the interaction of Cytotoxic T Lymphocyte Antigen (CTLA)-4 with CD80 is an antagonist to T cell activation. The new analysis provides information about free ligand diffusion in the contact area, the fraction of interactions that are stable and the kinetic off-rate. Independent data from equilibrium measurements are used to calculate the on-rate. The values for CD28-CD80 interaction reveal a 10-fold reduction in free CD80 diffusion, a small stable fraction of 9.6% and a 2D k/sub r/ of 0.057 s/sup -1/. This compares to an off-rate of 1.6 s/sup -1/ in solution, a difference of 30-fold. The CTLA-4-CD28 system is under analysis, but appears to have slower kinetics, requiring very long recovery time courses for analysis.