Document Detail


Type 1 diabetes: primary antigen/peptide/register/trimolecular complex.
MedLine Citation:
PMID:  22956469     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Type 1A diabetes (autoimmune) is now immunologically predictable in man, but preventable only in animal models. What triggers the development of autoimmunity in genetically susceptible individuals remains unknown. Studies of non-obese diabetic (NOD) mice reveal that interactions between T-cell receptors of diabetogenic T cell and an MHC class II loaded with an autoantigen are key determinates of the disease. With insulin as the primary target in the NOD mouse, likely man, and possibly the RT1-U rat models, therapeutic targeting of the components of these anti-insulin trimolecular complexes we believe provide a fulcrum for development of preventive therapy. In particular for the NOD mouse model, there is extensive evidence that the dominant insulin peptide driving disease initiation is insulin B chain amino acids 9-23 (SHLVEALYLVCGERG) recognized predominantly by germ-line sequences of a specific T-cell receptor Valpha (TRAV5D-4), and small molecules or monoclonal antibodies directed at this recognition complex can prevent diabetes.
Authors:
Tomasz Sosinowski; George S Eisenbarth
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Immunologic research     Volume:  55     ISSN:  1559-0755     ISO Abbreviation:  Immunol. Res.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-01-11     Completed Date:  2013-06-13     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8611087     Medline TA:  Immunol Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  270-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Autoantigens / immunology
Diabetes Mellitus, Type 1 / immunology*
Genes, MHC Class II
Humans
Peptides / immunology
Receptors, Antigen, T-Cell / immunology
Grant Support
ID/Acronym/Agency:
N01 AI 15416/AI/NIAID NIH HHS; P30 DK057516/DK/NIDDK NIH HHS; R01 DK 032083/DK/NIDDK NIH HHS; R01 DK032083/DK/NIDDK NIH HHS; U19AI050864/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Autoantigens; 0/Peptides; 0/Receptors, Antigen, T-Cell
Comments/Corrections

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