Checkpoints in the thymus for the control of autoimmunity: Antigen processing and regulatory T-cells

• Applicant: Professorin Dr. Eva Tolosa
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2004 to 2007
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5443925

Using myasthenia gravis (MG) and multiple sclerosis (MS) as model autoimmune diseases, this project will tackle two central aspects that affect the development of an autoimmune response: In the first place, we will study how immunogenic and tolerogenic epitopes are generated by the different antigen presenting cells in the human thymus. Taking myelin basic protein (MBP) and acetylcholine receptor (AchR) subunit polypeptides as model autoantigens and tetanus toxin (TT) as a foreign antigen, we will evaluate the proteolytic capabilities of thymic epithelial and dendritic cells, analyzing the fate of the most immunodominant epitopes for these antigens. On the other hand, we will study the mechanisms that fail to control autoreactive T cells which have escaped central tolerance. For this, we will evaluate the frequency, dynamics and function of T regulatory cells in patients with neurological autoimmune diseases.

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Arthur Melms