Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Autoantigens / immunology*
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / pathology
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COS Cells
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Clone Cells / immunology
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Clone Cells / pathology
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Cloning, Molecular
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Diabetes Mellitus, Type 1 / genetics
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Diabetes Mellitus, Type 1 / immunology*
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Epitopes, T-Lymphocyte / chemistry
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / immunology
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Gene Library*
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Histocompatibility Antigens Class I / immunology*
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Insulin / chemistry
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Insulin / genetics
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Insulin / immunology
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Interferon-gamma / biosynthesis
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Islets of Langerhans / immunology*
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Islets of Langerhans / metabolism
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Islets of Langerhans / pathology
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Lymphocyte Activation
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Lymphocyte Count
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Mice
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Mice, Inbred NOD
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Mice, Inbred Strains
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Organ Specificity
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Peptides / chemistry
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Peptides / genetics
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Peptides / immunology
Substances
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Autoantigens
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens Class I
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Insulin
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Peptides
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Interferon-gamma