Monoclonal antibody to rubella virus capsid protein recognizes a beta-cell antigen

The high frequency of insulin-dependent diabetes (IDDM) in children with congenital rubella suggests that the infectious agent may trigger the autoimmune process. To explore the immunologic relationship between rubella virus and IDDM, we examined a panel of mAb that recognizes rubella virus capsid and envelope glycoproteins for reactivity with islet cell Ag. One mAb, C9, which recognizes a defined domain within the capsid protein of rubella virus, was found to react with extracts from a rat beta-cell tumor and normal rat and human islets. Using one and two dimensional immunoblot analysis of rat beta-cell tumor extracts, the C9-like epitope was found to reside on a 52 kDa protein that is also the target of autoantibodies from human IDDM and nonobese diabetic mice. To confirm this cross-reactivity, antibodies in diabetic sera were absorbed to the recombinant rubella virus capsid protein, eluted, and then shown to react with the 52 kDa insulinoma protein. These data show that an immunogenic epitope on the rubella virus capsid protein is mimicked by a similar structure on a beta-cell protein. These findings suggest that rubella virus has the potential to sensitize susceptible individuals for an autoimmune response to beta-cell Ag and identify one mechanism that may contribute to beta destruction in IDDM.