Autoantigens Discovery and Characterization in Type 1 Diabetes
Type 1 diabetes is an autoimmune disease that is thought to be caused, in part, by a T cell-mediated destruction of insulin-producing β cells. High risk for disease, in those with genetic susceptibility, is predicted by the presence of two or more autoantibodies with different specificities. Autoantibodies against insulin, GAD65, IA-2, and ZnT8 are commonly known as the major specificities in type 1 diabetes. Despite this knowledge, we still do not know what leads to the breakdown of tolerance, and we have a poor understanding of type 1 diabetes etiology and pathophysiology. Several new autoantibodies have been recently discovered using innovative technologies, but neither their potential utility in monitoring disease development and treatment nor their role in the pathophysiology and etiology of type 1 diabetes has been explored.
The occurrence of post-translationally modified proteins (neoantigens) in autoimmune diseases such as rheumatoid arthritis and celiac disease is well documented. It was recently discovered that some T-cells in mouse models, as well as in people with type 1 diabetes, recognize neoantigens. If these altered self-proteins do not occur in the thymus, or are in other ways shielded from normal processes of peripheral self-tolerance, autoreactive T cells that recognize these peptides could be important for pathogenesis in type 1 diabetes. In addition, the endocrine function of the β cell and all its attendant processes, together with the pancreatic milieu, are increasingly thought to be associated with mechanisms of post-translational modification (for example, ER stress and microbiome interactions). Thus, continued identification and characterization of type 1 diabetes-relevant antigen epitopes for both autoantibodies and T cells is critically important for understanding the etiology and pathophysiology of type 1 diabetes. Characterization of these autoantigens could also bring new insights into the role of the islet autoimmunity in type 2 diabetes. Powerful new technologies provide opportunities to facilitate a more complete discovery and characterization of autoantigens, including hybrid peptides and post-translational modifications, and the immune response to them.
One of the goals of this workshop is to bring together investigators that use new methods and technologies to identify autoantigens and responses to them (antibodies or T cells). Researchers with diverse expertise will share ideas and identify resources. This could help them uncover opportunities to work together, to accelerate the progress of antigen/antigen response discovery and detection. The workshop could also bring in expertise to advise on next steps and help discoveries transition to utility as biomarkers of disease progression, treatment response, and ultimately, new antigen specific therapeutics.
Another goal of the workshop is to have a discussion on the progress and potential future development for: 1) The identification of new autoantigens and epitopes in type 1 diabetes; 2) The characterization of the response to new and previously known antigens (T-cell or humoral); and 3) The use of these antigens/epitopes and their response for identifying disease triggers and mechanisms, monitoring disease progression, and developing new treatments or preventative vaccines.
October 15, 2017
This meeting is being held in conjunction with the Workshop on Immune System Engineering for Targeted Tolerance in Type 1 Diabetes (T1D).