Modulation of TCR signaling and synapse formation by ectoenzymes and purinergic signals under physiological and pathological conditions

• Applicant: Professor Dr. Roland Martin
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Pharmacology
• Term: from 2009 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 86996090

The regulation of T cell signalling via purinergic signals has been well established in transformed cell lines. In contrast little is known regarding the sensitivity to purinergic signals alone and modulation via purines of signals induced through T cell receptor (TCR) and costimulatory molecules in human T cell clones that are specific for foreign and self antigens. According to the roles of purinergic signals in inflammatory contexts, it will be of interest to examine in well-characterized CD4+ T helper clones (Thl, Thl7) the roles of purinergic signals and their crosstalk with signal 1 (TCR) and costimulatory signals. Since the strength of the TCR-mediated signal plays an important role in the functional outcome of the stimulus with respect to full activation (agonist signal), partial activation (partial agonist) or even functional antagonization, we will perform signalling experiments and functional studies to address the influence of purinergic signals on the latter. Furthermore, the modulation of agonist signals is considered of particular relevance for the induction of central and also peripheral tolerance, and therefore we will examine whether purinergic stimuli play a role in modulating peripheral tolerance mechanisms. Finally, we will address whether the expression of ectoenzymes and purinergic signalling mechanisms are altered in a prototypical T cell-mediated autoimmune disease, multiple sclerosis.

• DFG Programme: Research Grants
• International Connection: Switzerland
• Participating Person: Professorin Dr. Eva Tolosa