Determinant spreading and the role of the MHC class II region in systemic and organ-specific autoimmunity

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Autoimmune diseases are among the most important group of disorders affecting the adult population. In these diseases the immune system damages organs and tissues producing widespread pathology (systemic autoimmunity such as Lupus erythematosus) or localised disease (organ-specific autoimmunity such as insulin dependent diabetes). We understand very little about how and why the immune system attacks the body's own tissues. This study examines how antibodies and T lymphocytes are formed against components located inside cells of the body. The study involves genetically modifying mice by introducing key human genes which influence the development of autoimmunity. In this way the role of these human genes can be examined experimentally without having to work exclusively on patients. We also hope that these mice might be important in creating new models of celiac disease and insulin dependent diabetes. The proposed experiments should tell us how these genes contribute to the development of autoimmune disease. This understanding could be relevant devising treatments and interventions to prevent autoimmune diseases.