BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:LAT signalling pathology: a T-cell dependent\, B cell autoimmune c ondition without T cell self-reactivity - P rofessor Bernard Malissen\, University of Marseille DTSTART:20121019T113000Z DTEND:20121019T123000Z UID:TALK40999@talks.cam.ac.uk CONTACT:Sue Griffin DESCRIPTION:When the T-cell receptor (TCR) recognizes antigens\, the CD3 c hains of the TCR complex are phosphorylated by the Src family kinase Lck. This allows the recruitment of the protein tyrosine kinase ZAP-70 that in turn phosphorylates several intracellular substrates\, including the LAT a daptor. Upon tyrosine phosphorylation\, LAT nucleates the assembly of a mu ltiprotein complex – the LAT signalosome – that bridges the T cell-spe cific and the ubiquitous components of the signaling pathways that control many aspects of T cell development and function. Partial loss-of-function mutations in several molecules involved in TCR signaling (ZAP-70\, LAT) r esult in inflammation and autoimmunity. \n\nHow can mutations that reduce TCR signaling output paradoxically lead to immune pathologies? We will sum marize recent data demonstrating that mutations in LAT predispose toward a berrant T cell responses to antigen in the presence of normal thymic selec tion. In the absence of LAT\, the activity of the Lck kinase appears susta ined without the need for TCR engagement.\n \nAs a consequence\, in the ab sence of LAT\, antigen-specific T cell responses evolve into pro-inflammat ory responses that unfold in a TCR-independent manner and induce the produ ction of autoantibodies in a “quasi-mitogenic” mode. Therefore\, some pathological conditions called "autoimmune" might not result from the pres ence of self-reactive T cells but from defect in mechanisms that normally keep protein tyrosine kinase activity in check.\n LOCATION:Lecture Theatre\, Department of Pathology\, Tennis Court Road END:VEVENT END:VCALENDAR