Characterization of the autoimmune response against the nerve tissue S 100β in patients with type 1 diabetes

Summary Type 1 diabetes results from destruction of insulin‐producing beta cells in pancreatic islets and is characterized by islet cell autoimmunity. Autoreactivity against non‐beta cell‐specific antigens has also been reported, including targeting of the calcium‐binding protein S 100β. In preclinical models, reactivity of this type is a key component of the early development of insulitis. To examine the nature of this response in type 1 diabetes, we identified naturally processed and presented peptide epitopes derived from S100β, determined their affinity for the human leucocyte antigen ( HLA)‐DRB1 *04:01 molecule and studied T cell responses in patients, together with healthy donors. We found that S100β reactivity, characterized by interferon ( IFN) ‐γ secretion, is a characteristic of type 1 diabetes of varying duration. Our results confirm S100β as a target of the cellular autoimmune response in type 1 diabetes with the identification of new peptide epitopes targeted during the development of the disease, and support the preclinical findings that autoreactivity against non‐beta cell‐specific autoantigens may have a role in type 1 diabetes pathogenesis.