Isolation of nonobese diabetic mouse T-cells that recognize novel autoantigens involved in the early events of diabetes

Diabetes. 1994 Jan;43(1):33-9. doi: 10.2337/diab.43.1.33.


Insulin-dependent diabetes mellitus (IDDM) is thought to result from chronic, cell-mediated, autoimmune islet damage. Our aim was to identify the earliest T-cell autoantigen in IDDM, reasoning that this antigen could be causally involved in the initiation of the disease. Identification of the earliest beta-cell-specific autoantigen is extremely important in allowing advances in prevention and treatment of initial events in the development of inflammatory insulitis that precedes beta-cell destruction and overt diabetes. Therefore, we analyzed the proliferative responses of peripheral T-cells from young, female nonobese diabetic (NOD) mice to extracts of pancreatic beta-cell lines. We were able to demonstrate that T-cells responsive to beta-cell antigens exist in the peripheral lymphoid tissue of these mice in the absence of deliberate priming before the manifestation of histologically detectable insulitis. T-cell lines and clones isolated from the peripheral lymphatic tissues of young, unimmunized, female NOD mice were also shown to react with extracts of beta-cells. Fractionation of the beta-cell extracts showed that these T-cell clones recognized multiple beta-cell-specific autoantigens but none of the previously reported putative autoantigens (glutamic acid decarboxylase [GAD]65, GAD67, Hsp65, insulin, ICA 69, carboxypeptidase-H, and peripherin). Thus, we can conclude that these responses are specific for novel beta-cell autoantigens. Finally, NOD T-cell proliferative responses were also seen to an extract of human islets suggesting potential shared antigenic determinants between human and mouse beta-cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

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

MeSH terms

  • Animals
  • Autoantigens / analysis*
  • Autoantigens / immunology
  • Base Sequence
  • Cell Line
  • DNA Primers
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Glutamate Decarboxylase / analysis
  • Glutamate Decarboxylase / biosynthesis
  • Glutamate Decarboxylase / immunology
  • Heat-Shock Proteins / analysis
  • Heat-Shock Proteins / biosynthesis
  • Heat-Shock Proteins / immunology
  • Islets of Langerhans / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred NOD / immunology*
  • Molecular Sequence Data
  • Pancreatic Diseases / immunology
  • Pancreatic Diseases / pathology
  • Polymerase Chain Reaction
  • T-Lymphocytes / immunology*


  • Autoantigens
  • DNA Primers
  • Heat-Shock Proteins
  • Glutamate Decarboxylase