characterization of signal transduction in autoreactive T-cells after stimulation with oligomerized T-cell receptor epitopes in models for demyelinating autoimmune diseases
Project management at the University of Würzburg:
Multiple sclerosis (MS) and Guillain-Barré-Syndrome (GBS) are demyelinating diseases of the nervous system with unknown etiology and pathogenesis. Autoreactive myelin specific T-lymphocytes and antibodies to myelin proteins are involved in the induction of these disorders. Experimental autoimmune encephalomyelitis (EAE) and neuritis (EAN) serve as animal models of MS and GBS and are used to analyze the pathogenesis of these diseases and to develop new therapies. Both experimental autoimmune diseases can be elicited by immunization with myelin proteins of the central (EAE) and peripheral (EAN) nervous system or by adoptive transfer of CD4+ T-helper cells specific for e.g. myelin basic protein (MBP) or P2 protein. Antigenic epitopes as well as T-cell receptor (TCR) usage are well characterized.Antigen therapy of EAE and EAN lead to specific termination of inflammatory reactions. Novel therapeutic approaches using oligomerized antigenic peptides have the potential to induce anergy or apoptosis of T-cells more efficiently and also over a longer time than previous approaches. The aim of this study is to modulate intracellular signal cascades after stimulation of autoreactive T-cells with various oligomerized TCR epitopes and to challenge new ways of therapeutic intervention.
Projekt period: from 05.1999 to 04.2004