Naturally processed T cell epitopes from human glutamic acid decarboxylase identified using mice transgenic for the type 1 diabetes- associated human MHC class II allele, DRB1*0401

Research output: Contribution to journalArticle


The identification of class II binding peptide epitopes from autoimmune disease-related antigens is an essential step in the development of antigen- specific immune modulation therapy. In the case of type 1 diabetes, T cell and B cell reactivity to the autoantigen glutamic acid decarboxylase 65 (GAD65) is associated with disease development in humans and in nonobese diabetic (NOD) mice. In this study, we identify two DRB1*0401-restricted T cell epitopes from human GAD65, 274-286, and 115-127. Both peptides are immunogenic in transgenic mice expressing functional DRB1*0401 MHC class II molecules but not in nontransgenic littermates. Processing of GAD65 by antigen presenting cells (APC) resulted in the formation of DRB1*0401 complexes loaded with either the 274-286 or 115-127 epitopes, suggesting that these naturally derived epitopes may be displayed on APC recruited into pancreatic islets. The presentation of these two T cell epitopes in the islets of DRB1*0401 individuals who are at risk for type 1 diabetes may allow for antigen-specific recruitment of regulatory cells to the islets following peptide immunization.


  • Linda S. Wicker
  • Shiow Ling Chen
  • Gerald T. Nepom
  • John F. Elliott
  • Daniel C. Freed
  • Alka Bansal
  • Song Zheng
  • Andrew Herman
  • Åke Lernmark
  • Dennis M. Zaller
  • Laurence B. Peterson
  • Jonathan B. Rothbard
  • Richard Cummings
  • Phyllis J. Whiteley
External organisations
  • Merck Research Laboratories
  • Washington University School of Medicine
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes


  • autoimmunity, diabetes mellitus, insulin-dependent, MHC class II, mice, inbred NOD, peptide autoantigens
Original languageEnglish
Pages (from-to)2597-2603
JournalJournal of Clinical Investigation
Issue number11
Publication statusPublished - 1996 Dec 1
Publication categoryResearch
Externally publishedYes