Our lab has been focused on the immunological synapse (figure, below) and integrating this into the 3D tissue context.
We have modeled this interaction by replacing the antigen presenting cell with a supported planar bilayer. Bilayers presenting MHC-peptide complexes and ICAM-1 to trigger a minimal immunological synapse.
This is an optically ideal system in which to visualize the supramolecular activation clusters. We have also applied this system to investigation of regulatory T cell defects in rheumatoid arthritis. Intravital microscopy has been a critical technology to understand how T cells interact with antigen presenting cells in vivo. Studies in T cell zones, germinal centers, meninges and splenic red pulp have provided novel insights.
In the future, we will address how the immunological synapse contributes to tolerance and immunity using tools of systems biology and super-resolution imaging.
We will continue to use intravital microscopy to probe inflammatory mechanisms (see movie, below). A major focus will be the targeting therapies to the immunological synapse to cure chronic inflammatory diseases like rheumatoid arthritis.
External collaborations
Skirball Institue of Biomolecular Medicine, New York
Nanomedicine Center for Mechanical Biology
Dr Iain Dunlop, Imperial College London
Michael Meyer-Hermann, Helmholtz, Braunschweig
Salvatore Valitutti, CRCT - INSERM
Cosima Baldari, University of Siena
Jens Rettig, University of Saarland
Projects
Immunological synapse derived ectosomes in T cell effector function
Understanding the immunological synapse is important for innovation in healthcare with the potential to lead to improved vaccines and immunotherapy.