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Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library [see comments]
Wong FS; Karttunen J; Dumont C; Wen L; Visintin I; Pilip IM; Shastri N;
December 30, 1999
Nat Med. 1999 Sep;5(9):1026-31. Unique Identifier : AIDSLINE

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.

JOURNAL ARTICLE Amino Acid Sequence Animal Autoantigens/*IMMUNOLOGY Clone Cells/IMMUNOLOGY/PATHOLOGY Cloning, Molecular CD8-Positive T-Lymphocytes/*IMMUNOLOGY/PATHOLOGY COS Cells Diabetes Mellitus, Insulin-Dependent/GENETICS/*IMMUNOLOGY Epitopes, T-Lymphocyte/CHEMISTRY/GENETICS/IMMUNOLOGY *Gene Library Histocompatibility Antigens Class I/*IMMUNOLOGY Insulin/CHEMISTRY/GENETICS/IMMUNOLOGY Interferon Type II/BIOSYNTHESIS Islets of Langerhans/*IMMUNOLOGY/METABOLISM/PATHOLOGY Lymphocyte Count Lymphocyte Transformation Mice Mice, Inbred NOD Mice, Inbred Strains Organ Specificity Peptides/CHEMISTRY/GENETICS/IMMUNOLOGY Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S.