Circulating Preproinsulin Signal Peptide–Specific CD8 T Cells Restricted by the Susceptibility Molecule HLA-A24 Are Expanded at Onset of Type 1 Diabetes and Kill β-Cells

• Published in: Diabetes (New York, N.Y.) Vol. 61; no. 7; pp. 1752 - 1759
• Main Authors: Kronenberg, Deborah, Knight, Robin R., Estorninho, Megan, Ellis, Richard J., Kester, Michel G., de Ru, Arnoud, Eichmann, Martin, Huang, Guo C., Powrie, Jake, Dayan, Colin M., Skowera, Ania, van Veelen, Peter A., Peakman, Mark
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.07.2012
• Subjects: Adult; Analysis; Autoantibodies - blood; Autoantibodies - immunology; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Cell Death - immunology; Cell Line; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epitopes, T-Lymphocyte - immunology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glutamate Decarboxylase - immunology; HLA class II antigens; HLA-A24 Antigen - immunology; Humans; Immunology and Transplantation; Insulin - blood; Insulin - immunology; Insulin-Secreting Cells - immunology; Male; Medical sciences; Middle Aged; Physiological aspects; Protein Precursors - blood; Protein Precursors - immunology; Protein Sorting Signals; T cells; Type 1 diabetes; Young Adult; Endocrinopathy; Immunopathology; HLA-System; Sensitivity; Peptides; Type 1 diabetes; Langerhans islet; T-Lymphocyte; Autoimmune disease; β Cell; Endocrine pancreas

Type 1 diabetes results from T cell-mediated β-cell destruction. The HLA-A*24 class I gene confers significant risk of disease and early onset. We tested the hypothesis that HLA-A24 molecules on islet cells present preproinsulin (PPI) peptide epitopes to CD8 cytotoxic T cells (CTLs). Surrogate β-cel...