| Autoreactive T-cell receptor (Vbeta/D/Jbeta) sequences in diabetes are homologous to insulin, glucagon, the insulin receptor, and the glucagon receptor. | |
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MedLine Citation:
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PMID: 19051206 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The hypervariable (Vbeta/D/Jbeta) regions of T-cell receptors (TCR) have been sequenced in a variety of autoimmune diseases by various investigators. An analysis of some of these sequences shows that TCR from both human diabetics and NOD mice mimic insulin, glucagon, the insulin receptor, and the glucagon receptor. Such similarities are not found in the TCR produced in other human autoimmune diseases. These data may explain how insulin, glucagon, and their receptors are targets of autoimmunity in diabetes and also suggest that TCR mimicking insulin and its receptor may be targets of anti-insulin autoantibodies. Such intra-systemic mimicry of self-proteins also raises complex questions about how "self" and "nonself" are regulated during TCR production, especially in light of the complementarity of insulin for its receptor and glucagon for its receptor. The data presented here suggest that some TCR may be complementary to other TCR in autoimmune diseases, a possibility that is experimentally testable. Such complementarity, if it exists, could either serve to down-regulate the clones bearing such TCR or, alternatively, trigger an intra-immune system civil war between them. |
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Authors:
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Robert Root-Bernstein |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of molecular recognition : JMR Volume: 22 ISSN: 1099-1352 ISO Abbreviation: J. Mol. Recognit. Publication Date: 2009 May-Jun |
Date Detail:
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Created Date: 2009-04-07 Completed Date: 2009-07-30 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9004580 Medline TA: J Mol Recognit Country: England |
Other Details:
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Languages: eng Pagination: 177-87 Citation Subset: IM |
Copyright Information:
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Copyright 2008 John Wiley & Sons, Ltd. |
Affiliation:
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Department of Physiology, 2174 Biomedical and Physical Sciences Building, Michigan State University, East Lansing, MI 48824, USA. rootbern@msu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Arthritis, Rheumatoid / immunology Diabetes Mellitus / immunology* Glucagon / chemistry* Hepatitis, Autoimmune / immunology Humans Insulin / chemistry* Mice Mice, Inbred NOD Molecular Sequence Data Myasthenia Gravis / immunology Peptides / chemistry Receptor, Insulin / chemistry* Receptors, Antigen, T-Cell, alpha-beta / chemistry* Receptors, Glucagon / chemistry* Sequence Homology, Amino Acid* |
| Chemical | |
Reg. No./Substance:
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0/Peptides; 0/Receptors, Antigen, T-Cell, alpha-beta; 0/Receptors, Glucagon; 11061-68-0/Insulin; 9007-92-5/Glucagon; EC 2.7.10.1/Receptor, Insulin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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