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

  • John A Gebe
  • Kellee A Unrath
  • Ben A Falk
  • Ito Kouichi
  • Li Wen
  • Terri L Daniels
  • Åke Lernmark
  • Gerald T Nepom
Publishing year: 2006
Language: English
Pages: 294-304
Publication/Series: Clinical Immunology1999-01-01+01:00
Volume: 121
Issue: 3
Document type: Journal article
Publisher: Elsevier

Abstract english

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


  • Immunology in the medical area
  • Diabetes
  • Tolerance
  • MHC
  • T cells
  • Transgenic


  • Diabetes and Celiac Unit
  • ISSN: 1521-6616
E-mail: ake [dot] lernmark [at] med [dot] lu [dot] se

Principal investigator

Diabetes and Celiac Unit

+46 40 39 19 01

+46 70 616 47 79


Jan Waldenströms gata 35, Malmö


Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00