Oral Presentation The Australasian Society for Immunology 2017 Annual Scientific Meeting

The immunological synapse and the structure of T cell communication (#5)

Michael Dustin 1 , David Saliba 1 , Philippos Demetriou 1 , Anastasios Siokis 2 , Ilenia Papa 3 , David Depoil 1 , Pablo Cespedes 1 , Stefan Balint 1 , Marion H. Brown 4 , Michael Meyer-Hermann 2 , Carola G. Vinuesa 3
  1. Kennedy Institute of Rheumatology , The University of Oxford, Oxford, United Kingdom
  2. Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany
  3. Department of Immunology and Infectious Diseases, Australian National University, Canberra, Australia
  4. Sir William Dunn School of Pathology, The University of Oxford, Oxford, United Kingdom

The interaction between a T cell and an antigen-presenting cell (APC) bearing agonist peptide-MHC complexes (pMHCAg) triggers signaling cascades that shape and are shaped by the Immunological Synapse (IS) a radially symmetric intercellular communication interface. During the formation of the IS, antigen (TCR), adhesion, co-stimulatory and co-inhibitory receptors are reorganized into specific patterns that rely on physical chemical principles and active transport.  We report to two novel structures that emerge from this process- synaptic ectosomes (SynEcts) and the adhesion corolla.  

Electron microscopy studies on IS formed by T cells on supported lipid bilayers (SLB) containing intercellular adhesion molecules-1 (ICAM1) and pMHCAg revealed the extrusion of SynEcts dependent upon Endosomal Sorting Complexes Required for Transport (ESCRT).   SynEcts are passed to the APC.  We have performed a more systematic analysis of SynEcts, including super-resolution fluorescence microscopy, and will report on distinct populations that incorporate critical components for T-APC communication.

The adhesion ring of the IS is composed on a course meshwork of integrins organized by actin-myosin arcs.  The integrin Lymphocyte Function Associated-1 (LFA1) interaction with its ligand ICAM1 segregates from the TCR-pMHCAg interactions, the latter fitting into openings in the mesh. Both the LFA1-ICAM1 and TCR-pMHCAg interactions are driven inward by actin-myosin based transport, with the ubiquitinated TCR being moved into SynEcts.  Another major adhesion system in humans is based on interaction of the immunoglobulin superfamily members CD2 and CD58, which self-assemble large adhesion zones in an energy independent manner.  The CD2-CD58 interaction readily co-localizes with TCR-pMHC interactions.  We will present experimental and modelling results on how CD2-CD58 interactions organise into a corolla structure in the periphery of the immunological synapse.  Additional data will be presented on the implications of the corolla mechanism for co-stimulation and co-inhibition.