Conserved T cell receptor alpha-chain induces insulin autoantibodies.
basic_science · Level V
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- Record sourced from PubMed, PMID 18626021.
- Also identified by DOI 10.1073/pnas.0801648105 and PMC identifier 2464615.
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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.
Medical subject headings
- Autoantibodies
- Genes, T-Cell Receptor alpha
- Insulin
- Insulin Antibodies