Super-Resolution Imaging of T Cell Triggering Supports the Kinetic Segregation Model in the Adaptive Immune Response

Among the most contentious questions in immunology is: how is the T cell receptor (TCR) triggered? using a combination of different single-molecule tracking, novel calcium signalling assays, crystallography and super-resolution imaging techniques we have demonstrated evidence to support the kinetic segregation model as the molecular mechanism behind the adaptive immune system.The phosphorylation of the T cell receptor is required for T cell activation. The kinetic segregation model predicts that this is achieved by the spatial partitioning of important components such as the TCR and Lck kinase from the CD45 phosphatase according to the difference in size of the extracellular domain of the proteins on the cell membrane. We test this prediction by imaging the formation of contacts between T cells with a model antigen presenting cells in early stage contacts at endogenous expression levels. The approach allows the interrogation of the kinetic segregation with other models based upon aggregation or conformation change of the TCR. We present the results of this study.