Immunological synapse derived ectosomes in T cell effector function

The immunological synapse is a highly conserved scaffold for communication between immune cells built around cooperation of antigen and adhesion receptors. It often takes the form of a bull’s eye with a central cluster of antigen receptors surrounded by a ring of adhesion molecules. We have recently observed that antigen receptor coated extracellular microvesicles bud directly from the center of the immunological synapse- which we define as synaptic ectosomes. Synaptic ectosomes are transferred to the antigen- presenting cell and can generate signals after the T cell-APC synapse has dissolved. We aim to determine the composition of synaptic ectosomes, determine their fate in the antigen-presenting cell and identify approaches to manipulate their formation in vivo. The objectives will be to 1) isolate synaptic ectosomes from human T cells and determine their molecular composition; 2) determine the functional impact of synaptic ectosomes on the antigen presenting cell; and 3) use gene targeting to control the process in vivo to understand its role in T function of helper, cytotoxic and regulatory T cells. The technologies will include microscopy, proteomics, genomics, and in vivo models with constitutive and conditional gene targeting. This work will address fundamental gaps in our understanding of immune cell communication.