| Suppressive effect of glutamic acid decarboxylase 65-specific autoimmune B lymphocytes on processing of T cell determinants located within the antibody epitope. | |
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MedLine Citation:
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PMID: 12097368 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Type 1 diabetes is a T cell-mediated disease in which B cells serve critical Ag-presenting functions. In >95% of type 1 diabetic patients the B cell response to the glutamic acid decarboxylase 65 (GAD65) autoantigen is exclusively directed at conformational epitopes residing on the surface of the native molecule. We have examined how the epitope specificity of Ag-presenting autoimmune B cell lines, derived from a type 1 diabetic patient, affects the repertoire of peptides presented to DRB1*0401-restricted T cell hybridomas. The general effect of GAD65-specific B cells was to enhance Ag capture and therefore Ag presentation. The enhancing effect was, however, restricted to T cell determinants located outside the B cell epitope region, because processing/presentation of T cell epitopes located within the autoimmune B cell epitope were suppressed in a dominant fashion. A similar effect was observed when soluble Abs formed immune complexes with GAD65 before uptake and processing by splenocytes. Thus, GAD65-specific B cells and the Abs they secrete appear to modulate the autoimmune T cell repertoire by down-regulating T cell epitopes in an immunodominant area while boosting epitopes in distant or cryptic regions. |
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Authors:
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Juan Carlos Jaume; Sarah Louise Parry; Anne-Marie Madec; Grete Sønderstrup; Steinunn Baekkeskov |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 169 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2002 Jul |
Date Detail:
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Created Date: 2002-07-04 Completed Date: 2002-08-28 Revised Date: 2007-10-24 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 665-72 Citation Subset: AIM; IM |
Affiliation:
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Diabetes Center, Department of Medicine, Division of Endocrinology and Metabolism, Department of Veterans Affairs Medical Center and University of California, San Francisco, CA 94143, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Antigen Presentation / immunology* Antigen-Antibody Complex / immunology, metabolism Autoantibodies / chemistry, metabolism*, pharmacology Autoantigens / immunology*, metabolism, pharmacology B-Lymphocyte Subsets / enzymology, immunology*, metabolism Binding Sites, Antibody / immunology Cell Line, Transformed Dendritic Cells / immunology, metabolism Down-Regulation / immunology* Epitopes, B-Lymphocyte / immunology*, metabolism, pharmacology Epitopes, T-Lymphocyte / immunology, metabolism* Glutamate Decarboxylase / immunology*, metabolism, pharmacology Humans Immunosuppressive Agents / chemistry, metabolism, pharmacology Isoenzymes / immunology*, metabolism, pharmacology Macrophages / immunology, metabolism Mice Mice, Transgenic Molecular Sequence Data Protein Binding / immunology Receptors, Antigen, B-Cell / metabolism T-Lymphocyte Subsets / immunology, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antigen-Antibody Complex; 0/Autoantibodies; 0/Autoantigens; 0/Binding Sites, Antibody; 0/Epitopes, B-Lymphocyte; 0/Epitopes, T-Lymphocyte; 0/Immunosuppressive Agents; 0/Isoenzymes; 0/Receptors, Antigen, B-Cell; EC 4.1.1.15/Glutamate Decarboxylase; EC 4.1.1.15/glutamate decarboxylase 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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