The immunological synapse: Pattern formation and recognition of non-self

Cell-cell interaction between immune cells often involves formation of an organized pattern of surface molecules in the intercellular junction. Recent experiments demonstrate interesting spatio-temporal evolution of patterns of different receptors and ligands complexes between T cells and antigen presenting cells(APC). This is called the immunological synapse, and it is hypothesized to be implicated in mature T cell activation. Mature T cell activation and selection of immature T cells (thymocytes) are both initiated by binding of TCR molecules on the surface of T cells to MHC-peptide molecules on the surface of antigen presenting cells. The biological outcome, however, is vastly different in the two cases: proliferation of mature T cells versus apoptosis during negative selection of thymocyte. The spatial pattern of receptors and ligands in the thymocyte immunological synapse is different during thymocyte selection compared to mature T cell activation. Recently, a synapse assembly model has been proposed that enables calculation of the propensity for synapse assembly driven by membrane-constrained protein binding interactions. Using this model, we show that lower TCR expression in thymocytes and thermal cell membrane fluctuations contribute to affecting these differences. We also find that predictions of mature T cell synapse assembly, based on TCR/MHC-peptide binding kinetics, correlate well with observed cytokine responses by T cells bearing the relevant TCR, but not with CTL mediated killing. This suggests a different role for the synapse in pre- and post-nuclear activation events in T-cells. We have also studied the effects of concentration of pMHC and ICAM-1 on the efficacy of synapse formation. Our most interesting finding is that the range of pMHC concentrations over which stable synapses can form depends in a sensitive way on receptor-ligand binding strength.