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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.

Original publication

DOI

10.1172/jci119079

Type

Journal article

Journal

The Journal of clinical investigation

Publication Date

12/1996

Volume

98

Pages

2597 - 2603

Addresses

Department of Autoimmune Diseases Research, Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA. linda_wicker@merck.com

Keywords

B-Lymphocytes, T-Lymphocytes, Cell Line, Animals, Mice, Inbred NOD, Mice, Transgenic, Humans, Mice, Diabetes Mellitus, Type 1, Glutamate Decarboxylase, Peptide Fragments, Recombinant Proteins, Autoantibodies, HLA-DR Antigens, Epitopes, Lymphocyte Activation, Genes, MHC Class II, Amino Acid Sequence, Alleles, Molecular Sequence Data, HLA-DRB1 Chains