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

Nat Med. 1999 Sep;5(9):1026-31. doi: 10.1038/12465.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoantigens / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • COS Cells
  • Clone Cells / immunology
  • Clone Cells / pathology
  • Cloning, Molecular
  • 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

Substances

  • Autoantigens
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class I
  • Insulin
  • Peptides
  • Interferon-gamma