Séminaire CIRI : Pr. Michaël L. DUSTIN

Pr. Michaël L DUSTIN (Kennedy Institute of Rheumatology, University of Oxford - GB): "Supramolecular assemblies in the immunological synapse"

Abstract: In this talk I will provide a historical background on immunological synapses and then discuss three ongoing stories. We started our analysis of supramolecular assemblies in the immunological synapse through study of CD4 helper T cells- first looking at signaling through antigen receptors and then the fate of those receptors in extracellular vesicles created by T cell at the synaptic interface to coordinate immune responses.  We next adapted our technology to investigated how CD8 cytotoxic T cells and NK cells us supramolecular assemblies to kill infected and cancerous cells.  Which cytotoxic mechanisms are deployed is tactical and basic on what target-associated receptors are discovered by the T cell.  FAS on targets triggered extracellular vesicles with FasL to trigger target suicide, whereas 100 nm protein “bombs” with a core of cytotoxic perforin and granzymes and a shell of thrombospondin-1 were deployed when the target expressed ICAM1 or CD47.  We refer to these protein bombs as supramolecular attack particles and these have potential as novel therapeutics.  Finally, I will discuss how malaria parasites use some members of a large family of proteins called RIFINs to inhibit attack by innate natural killer (NK) cells-creating an inhibitory immunological synapse to protect parasitized red blood cells.  In order to defeat this mechanism, the host makes extraordinary antibodies that incorporate entire RIFIN targets into antibody V-regions.