Molecular mimicry: anti-DNA antibodies may arise inadvertently as a response to antibodies generated to microorganisms

The origin of anti-DNA antibodies remains speculative. We argue that some of these antibodies may arise inadvertently in nature during the course of a normal immune response due to their induction by antibodies which bear structures (mimotopes) that mimic DNA. These antibodies are not necessarily DNA specific but, like the T15 idiotype (id)-positive antibodies which bind to phosphorylcholine, are produced normally to some environmental or microbial antigen. Such a mimotope was found in a T15(+) antibody at the highly specific region encoded principally by the D gene, DFL16.1. This mimotope was also found in human antibodies that are encoded by DXP'1, the human counterpart of DFL16.1 and which is used commonly in anti-DNA antibodies. The mimotope is closely related to the epitope responsible for the T15 id and appears to be cryptic or normally hidden in the native protein. The existence of such a common, conserved sequence raises questions about how easily anti-DNA antibodies can be generated in nature and what purpose these proteins may serve. Molecular mimicry with regard to autoimmunity must thus be viewed as existing not necessarily between the infectious agent and self-antigens, but also between the antibodies induced by the organism and the self-antigens.