Induction, acceleration or prevention of autoimmunity by molecular mimicry

The hypothesis that cross-reactivity between microbial and self determinants recognized by the adaptive immune system could induce autoimmune diseases is very intriguing. However, definite proof in humans is very difficult to achieve and evidence is frequently circumstantial. Therefore, animal models are instrumental for understanding, how and when mimicry could be involved in the pathogenesis of autoimmunity. In this article, we will discuss experimental scenarios, where mimicry between foreign and self determinants does not cause disease per se, but rather aggravates a pre-existing yet sub-clinical autoimmune condition. We would like to propose that molecular mimicry is more likely to impact on an already existing autoimmune process rather than precipitate novel disease by breaking of tolerance from the beginning. Already activated autoreactive cells might be easier re-activated and primed for effector functions by cross-reactive ligands than naive lymphocytes. (C) 2003 Elsevier Ltd. All rights reserved.