期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2008
卷号：105
期号：29
页码：10090-10094
DOI：10.1073/pnas.0801648105
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 V{alpha}-segment/J{alpha}-segment, but no conservation of the {alpha}-chain N region and no conservation of the V{beta}-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 V{beta}. 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.
关键词：autoimmunity ; NOD mouse ; Type 1 diabetes ; retrogenic
