Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice.

Research output: Contribution to journalArticle


We have identified for the first time an age-dependent spontaneous loss of tolerance to two self-antigenic epitopes derived from putative diabetes-associated antigens glutamic acid decarboxylase (GAD65) and glial fibrillary acidic protein (GFAP) in RIP-B7/DRB1*0404 HLA transgenic mice. Diabetic and older non-diabetic mice exhibited a proliferative response to an immunodominant epitope from GAD65 (555-567) and also from GFAP (240-252) but not from an immunogenic epitope from diabetes-associated islet-specific glucose-6-phosphatase catalytic subunit-related protein. The response to both of these self-antigens is not observed in young mice but is observed in older non-diabetic mice and is accompanied by histological evidence of insulitis in the absence of overt diabetes. Islet infiltrates in older non-diabetic mice and diabetic mice contain CD4(+)/FoxP3(+) cells and suggest the presence of a regulatory mechanism prior and during diabetic disease. Diabetes penetrance in RIP-B7/DR0404 mice


  • John A Gebe
  • Kellee A Unrath
  • Ben A Falk
  • Ito Kouichi
  • Li Wen
  • Terri L Daniels
  • Åke Lernmark
  • Gerald T Nepom
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area


  • Diabetes, Tolerance, MHC, T cells, Transgenic
Original languageEnglish
Pages (from-to)294-304
JournalClinical Immunology
Issue number3
Publication statusPublished - 2006
Publication categoryResearch