Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library

• Published in: Nature medicine Vol. 5; no. 9; pp. 1026 - 1031
• Main Authors: Wong, F. Susan, Karttunen, Jaana, Dumont, Caroline, Wen, Li, Visintin, Irene, Pilip, Ingrid M, Shastri, Nilabh, Pamer, Eric G, Janeway, Charles A
• Format: Journal Article
• Language: English
• Published: United States 01.09.1999
• Subjects: AIDS/HIV; Amino Acid Sequence; Animals; Autoantigens - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Clone Cells - immunology; Clone Cells - pathology; Cloning, Molecular; COS Cells; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Gene Library; Histocompatibility Antigens Class I - immunology; Insulin - chemistry; Insulin - genetics; Insulin - immunology; Interferon-gamma - biosynthesis; Islets of Langerhans - immunology; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Lymphocyte Activation; Lymphocyte Count; Mice; Mice, Inbred NOD; Mice, Inbred Strains; Organ Specificity; Peptides - chemistry; Peptides - genetics; Peptides - immunology
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/12465

Type 1 diabetes is an autoimmune disease in which the insulin-producing pancreatic beta cells are destroyed at an early age by an immune process that involves both CD4 and CD8 T lymphocytes. The identification of autoantigens in diabetes is very important for the design of antigen-specific immunotherapy. By screening a pancreatic islet cDNA library, we have identified the autoantigen recognized by highly pathogenic CD8 T cells in the non-obese diabetic mouse, one of the best animal models for human diabetes. This is the first identification, to our knowledge, of a CD8 T-cell epitope in an autoimmune disease. The peptide recognized by the cells is in the same region of the insulin B chain as the epitope recognized by previously isolated pathogenic CD4 T cells. This has very important implications for the potential use of insulin in preventative therapy.