Immunological synapse derived ectosomes in T cell effector function: SYNECT

Programme(s): H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
Topic(s): ERC-ADG-2014 - ERC Advanced Grant
Call for proposal: ERC-2014-ADG
Funding Scheme: ERC-ADG - Advanced Grant

Grant agreement ID: 670930

Objective
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.