Molecular Mimicry - Epitope Spreading

Epitope Spreading

Epitope spreading is another common way in which autoimmunity can occur which uses the molecular mimicry mechanism. This inducer of autoimmunity causes autoreactive T cells to be activated de novo by self epitopes released secondary to pathogen-specific T cell-mediated bystander damage. T cell responses to progressively less dominant epitopes are activated as a consequence of the release of other antigens secondary to the destruction of the pathogen with a homologous immunodominant sequence. Thus, inflammatory responses induced by specific pathogens that trigger pro-inflammatory T_h1 responses have the ability to persist in genetically susceptible hosts. This may lead to organ-specific autoimmune disease. Conversely, epitope spreading could be due to target antigens being physically linked intracellularly as members of a complex to self antigen. The result of this is an autoimmune response that is triggered by exogenous antigen that progresses to a truly autoimmune response against mimicked self antigen and other antigens. From these examples, it is clear that the search for candidate mimic epitopes must extend beyond the immunodominant epitopes of a given autoimmune response.