Possible mechanisms of autoantibody production and the connection of viral infections in human autoimmune diseases.

The presence of autoantibodies is a characteristic phenomenon in an autoimmune disease. In order to investigate the mechanisms of the autoantibody production, we have performed epitope mappings of the autoantigens. It thus was found that there were multiple epitopes on an autoantigen molecule, and a serum from a patient with an autoimmune disease usually recognizes these multiple epitopes simultaneously, suggesting that autoantibodies are ultimately produced by an antigen-driven mechanism. However, other evidence suggests that tolerance to a self antigen is rather tightly maintained and a simple antigen-driven mechanism cannot easily take place. Based on the results of epitope mappings, it appears that there is a major or a usually recognized epitope on almost every autoantigen molecule. Some patients only recognize this epitope. It is unlikely that only a single epitope can be recognized if a large molecule is immunized to the host. Therefore, the recognition of this universal epitope may play some roles in the induction of the autoantibody production. In fact, some of these epitopes have sequences homologous to those of viral proteins. Thus, it is possible that an immune response to a certain virus might induce by molecular mimicry the recognition of an autoantigen. Possible mechanisms following this molecular mimicry that may induce antigen-driven autoantibody production are discussed.