Associated TP24: T cell receptor repertoire in experimental epidermolysis bullosa acquisita

Chronic inflammation in autoimmune diseases is caused by a dysregulated immune system and a loss of tolerance to autoantiges. One typical example of a chronic autoimmune disease is EBA. The clinical manifestation of EBA is characterized by the production of complement activating autoantibodies targeting type VII collagen, an integral element of the dermal-epidermal junction. Experimental studies, focusing on the development of EBA, identified CD4+ T helper cells as necessary and key contributors in EBA formation. In   general, the importance of T cells in inflammation is well characterized although, information about the T cell receptor repertoire in immune-mediated disorders such as EBA is lacking. Based on the huge variety of the potential antigen receptors and subsequently T cells, an analysis of the exact adaptive immune repertoire was not feasible in the past. With ongoing development in the field of next-generation sequencing (NGS), with focus on the T cell receptors  α and β chains, deep sequencing of the highly variable complementary-determining region 3 (CDR3) region was enabled.

The main goal of this project is the identification of the T cell receptor repertoire in inflammatory autoimmune diseases and to evaluate processes possibly leading to disease manifestation. In order to achieve this, the CDR 3 region of the T cell receptor β chains in germinal centers and affected skin areas is analyzed via NGS and evaluated by bioinformatic analysis. This might enable the identification of autoreactive T cell receptors, conducting the loss of tolerance.