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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

Wicker, Linda S. ; Chen, Shiow Ling ; Nepom, Gerald T. ; Elliott, John F. ; Freed, Daniel C. ; Bansal, Alka ; Zheng, Song ; Herman, Andrew ; Lernmark, Åke LU orcid and Zaller, Dennis M. , et al. (1996) In Journal of Clinical Investigation 98(11). p.2597-2603
Abstract

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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
autoimmunity, diabetes mellitus, insulin-dependent, MHC class II, mice, inbred NOD, peptide autoantigens
in
Journal of Clinical Investigation
volume
98
issue
11
pages
2597 - 2603
publisher
The American Society for Clinical Investigation
external identifiers
  • scopus:10544223741
  • pmid:8958223
ISSN
0021-9738
DOI
10.1172/JCI119079
language
English
LU publication?
no
id
c1f7e368-9df0-46de-9a28-8acd548b9440
date added to LUP
2019-07-01 13:21:25
date last changed
2024-06-25 22:19:32
@article{c1f7e368-9df0-46de-9a28-8acd548b9440,
  abstract     = {{<p>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.</p>}},
  author       = {{Wicker, Linda S. and Chen, Shiow Ling and Nepom, Gerald T. and Elliott, John F. and Freed, Daniel C. and Bansal, Alka and Zheng, Song and Herman, Andrew and Lernmark, Åke and Zaller, Dennis M. and Peterson, Laurence B. and Rothbard, Jonathan B. and Cummings, Richard and Whiteley, Phyllis J.}},
  issn         = {{0021-9738}},
  keywords     = {{autoimmunity; diabetes mellitus, insulin-dependent; MHC class II; mice, inbred NOD; peptide autoantigens}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{11}},
  pages        = {{2597--2603}},
  publisher    = {{The American Society for Clinical Investigation}},
  series       = {{Journal of Clinical Investigation}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1172/JCI119079}},
  doi          = {{10.1172/JCI119079}},
  volume       = {{98}},
  year         = {{1996}},
}