Conserved T cell receptor alpha-chain induces insulin autoantibodies |
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Authors: | Kobayashi Masakazu Jasinski Jean Liu Edwin Li Marcella Miao Dongmei Zhang Li Yu Liping Nakayama Maki Eisenbarth George S |
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Affiliation: | Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Aurora, CO 80045, USA. |
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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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Keywords: | autoimmunity NOD mouse Type 1 diabetes retrogenic |
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