Selection of antigen epitopes

Selection of autoantigen epitopes by antigen presenting cells in the human thymus

A large number of peripheral autoantigens are expressed in the thymus, and a correlation between the lack of a certain epitope in the thymus and the development of autoimmune disease has already been established. How a balance is achieved between the generation of suitable peptides versus their destruction in the proteolytic environment of the lysosomes is not yet known. This issue is of particular importance in the antigen presenting cells (APC) of the thymus, where an excess of proteolysis could lead to a breakdown of tolerance to self-peptides and thus autoimmunity.
We plan to use recombinant autoantigens (MBP, AchR, MOG)  for digestion using lysosomal contents of different thymic antigen processing cells, and compare the peptides obtained with those coming from peripheral antigen presenting cells. We will specially focus in the creation and destruction of those immunodominant epitopes with are known to be of importance in autoimmune disease.

Contact: E. Tolosa, C. Stöckle