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| Article Authors: | Masakazu Kobayashi; Jean Jasinski; Edwin Liu; Marcella Li; Dongmei Miao; Li Zhang; Liping Yu; Maki Nakayama; George S Eisenbarth |
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| Article Title: | Conserved T cell receptor alpha-chain induces insulin autoantibodies. |
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| Reference ID: | 1013546 |
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| Abstract: | A fundamental question is what are the molecular determinants that lead to spontaneous preferential targeting of specific autoantigens in autoimmune diseases, such as the insulin B:9-23 peptide sequence in type 1 diabetes. Anti-insulin B:9-23 T cell clones isolated from prediabetic NOD islets have a conserved Valpha-segment/Jalpha-segment, but no conservation of the alpha-chain N region and no conservation of the Vbeta-chain. Here, we show that the conserved T cell receptor alpha-chain generates insulin autoantibodies when transgenically or retrogenically introduced into mice without its corresponding Vbeta. We suggest that a major part of the mystery as to why islet autoimmunity develops relates to recognition of a primary insulin peptide by a conserved alpha chain T cell receptor. |
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| Affiliations: | Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Aurora, CO 80045, USA. |
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| Date: | 2008 |
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| Reference Type: | Literature |
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| PubMed ID: | 18626021 |
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| Journal: | Proc Natl Acad Sci U S A |
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| Journal Volume: | 105 |
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| Article Pages: | 10090-4 |
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| Journal ISSN: | 1091-6490 |
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| Article Chemical List: | Autoantibodies;DNA Primers;Insulin Antibodies;Receptors, Antigen, T-Cell, alpha-beta;Insulin;Interferon-gamma |
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| Article MeSH List: | Adoptive Transfer; Animals; Autoantibodies(biosynthesis); Base Sequence; Clone Cells(immunology); Conserved Sequence; DNA Primers(genetics); Female; Genes, T-Cell Receptor alpha; Genes, T-Cell Receptor beta; Insulin(immunology); Insulin Antibodies(biosynthesis); Interferon-gamma(biosynthesis); Islets of Langerhans(immunology; pathology); Male; Mice; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Mice, Transgenic; Receptors, Antigen, T-Cell, alpha-beta(genetics; metabolism); T-Lymphocytes(immunology) |
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| Curation Last Updated: | 2011-08-24 00:17:28 |
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