A disease-associated cellular immune response in type 1 diabetics to an immunodominant epitope of insulin

J Clin Invest. 2001 Jan;107(2):173-80. doi: 10.1172/JCI8525.


The 9-23 amino acid region of the insulin B chain (B9-23) is a dominant epitope recognized by pathogenic T lymphocytes in nonobese diabetic mice, the animal model for type 1 diabetes. We describe herein similar (B9-23)-specific T-cell responses in peripheral lymphocytes obtained from patients with recent-onset type 1 diabetes and from prediabetic subjects at high risk for disease. Short-term T-cell lines generated from patient peripheral lymphocytes showed significant proliferative responses to (B9-23), whereas lymphocytes isolated from HLA and/or age-matched nondiabetic normal controls were unresponsive. Antibody-mediated blockade demonstrated that the response was HLA class II restricted. Use of the highly sensitive cytokine-detection ELISPOT assay revealed that these (B9-23)-specific cells were present in freshly isolated lymphocytes from only the type 1 diabetics and prediabetics and produced the proinflammatory cytokine IFN-gamma. This study is, to our knowledge, the first demonstration of a cellular response to the (B9-23) insulin epitope in human type 1 diabetes and suggests that the mouse and human diseases have strikingly similar autoantigenic targets, a feature that should facilitate development of antigen-based therapeutics.

MeSH terms

  • Adolescent
  • Adult
  • Cells, Cultured
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Humans
  • Immunodominant Epitopes / pharmacology
  • Insulin / pharmacology*
  • Interferon-gamma / immunology
  • Lymphocyte Activation / drug effects
  • Male
  • Peptide Fragments / pharmacology*
  • Prediabetic State / blood
  • Prediabetic State / immunology*
  • Risk Factors
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology


  • Immunodominant Epitopes
  • Insulin
  • Peptide Fragments
  • insulin B (9-23)
  • Interferon-gamma