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.
Wicker, Linda S.; Chen, Shiow-Ling; Nepom, Gerald T.; Elliott, John F.; Freed, Daniel C.; Bansal, Alka; Zheng, Song; Herman, Andrew; Lernmark, Ake; Zaller, Dennis M.; Peterson, Laurence B.; Rothbard, Jonathan B.; Cummings, Richard; Whiteley, Phyllis J.
[Article] Journal of Clinical Investigation. 98(11):2597-2603, December 1, 1996.

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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. (J. Clin. Invest. 1996. 98:2597-2603.)

Copyright (C) 1996 The American Society for Clinical Investigation, Inc.