title: Characterization of the autoimmune response against the nerve tissue S100β in patients with type 1 diabetes.
abstract: 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 S100β. 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Gómez-Touriño
authors.forename: R
authors.initials: R
authors.lastname: Simón-Vázquez
authors.forename: J
authors.initials: J
authors.lastname: Alonso-Lorenzo
authors.forename: S
authors.initials: S
authors.lastname: Arif
authors.forename: C
authors.initials: C
authors.lastname: Calviño-Sampedro
authors.forename: Á
authors.initials: Á
authors.lastname: González-Fernández
authors.forename: E
authors.initials: E
authors.lastname: Pena-González
authors.forename: J
authors.initials: J
authors.lastname: Rodríguez
authors.forename: J
authors.initials: J
authors.lastname: Viñuela-Roldán
authors.forename: J
authors.initials: J
authors.lastname: Verdaguer
authors.forename: O J
authors.initials: OJ
authors.lastname: Cordero
authors.forename: M
authors.initials: M
authors.lastname: Peakman
authors.forename: R
authors.initials: R
authors.lastname: Varela-Calvino
mesh_terms: D001324:Autoantigens / Q000276:immunology; D001483:Base Sequence; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D005260:Female; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D064568:S100 Calcium Binding Protein beta Subunit / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; C573415:IFNG protein, human; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D007371:Interferon-gamma
keywords: S100β; Th1; autoimmunity; peptide epitopes; type 1 diabetes