Figure 3.

Molecular mimicry, remnant epitopes and infections in VKH disease, as an example of autoimmunity. Two basic mechanisms of autoimmunity, molecular mimicry indicated at the right side (44) and remnant epitopes indicated at the left side (20) are compared. For the development of adaptive immune responses (indicated centrally at the bottom and between double braces), two signals are necessary (34). The so-called “signal 1” is the antigenic stimulus, which in the cases of autoimmune processes is an autoantigen, eliciting B cell or T cell responses through their cognate receptors (BCR and TCR). “Signal 2” is in most cases an environmental signal from an infection, which is translated at the molecular level into cell adhesion molecules or cytokines as reinforcers of the actions of the immunological synapse between an antigen-presenting cell (APC) and a T cell or in the activation of B cells. In the situation of molecular mimicry (44), the infection itself provides both the antigenic stimulus and the activation of adaptive immune cells. In this case “Signal 1” and “Signal 2” have the same origin and structural resemblance between a host autoantigen and a microbial epitope leads to cross-reactive “signal 1.” In the cases of remnant epitopes, various forms of infections may provide direct proteolysis and posttranslational modifications or induce host proteases and other enzymes. Their concerted actions lead to the generation of collections of autoantigenic peptides with an enhanced propensity to provide “signal 1,” when compared to healthy conditions. When this happens in the context of an infection or inflammation, the required “signal 2” is also present. Figure adapted from reference (20).