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.

L S Wicker; S L Chen; G T Nepom; J F Elliott; D C Freed; A Bansal; S Zheng; A Herman; A Lernmark; D M Zaller; L B Peterson; J B Rothbard; R Cummings; P J Whiteley

doi:10.1172/JCI119079

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

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

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

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

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

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

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

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

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

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

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

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

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

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Published in Volume 98, Issue 11 on December 1, 1996
J Clin Invest. 1996;98(11):2597–2603. https://doi.org/10.1172/JCI119079.
© 1996 The American Society for Clinical Investigation

Published December 1, 1996 - Version history

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.

Version 1 (December 1, 1996): No description

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.

L S Wicker, S L Chen, G T Nepom, J F Elliott, D C Freed, A Bansal, S Zheng, A Herman, A Lernmark, D M Zaller, L B Peterson, J B Rothbard, R Cummings, and P J Whiteley

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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.

L S Wicker, S L Chen, G T Nepom, J F Elliott, D C Freed, A Bansal, S Zheng, A Herman, A Lernmark, D M Zaller, L B Peterson, J B Rothbard, R Cummings, and P J Whiteley

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