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Åke Lernmark

Principal investigator

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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

Author

  • 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

Summary, in English

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.

Publishing year

1996-12-01

Language

English

Pages

2597-2603

Publication/Series

Journal of Clinical Investigation

Volume

98

Issue

11

Document type

Journal article

Publisher

Am Soc Clin Investig

Topic

  • Endocrinology and Diabetes

Keywords

  • autoimmunity
  • diabetes mellitus, insulin-dependent
  • MHC class II
  • mice, inbred NOD
  • peptide autoantigens

Status

Published

ISBN/ISSN/Other

  • ISSN: 0021-9738