Molecular mimicry: Can epitope mimicry induce autoimmune disease?

Abstract

Mimicry of host antigens by infectious agents may induce cross‐reactive autoimmune responses to epitopes within host proteins which, in susceptible individuals, may tip the balance of immunological response versus tolerance toward response and subsequently lead to autoimmune disease. Epitope mimicry may indeed be involved in the pathogenesis of several diseases such as post‐viral myocarditis or Chagas disease, but for many other diseases in which it has been implicated, such as insulin‐dependent diabetes mellitis or rheumatoid arthritis, convincing evidence is still lacking. Even if an epitope mimic can support a cross‐reactive T or B cell response in vitro, its ability to induce an autoimmune disease in vivo will depend upon the appropriate presentation of the mimicked host antigen in the target tissue and, in the case of T cell mimics, the ability of the mimicking epitope to induce a proliferative rather than anergizing response upon engagement of the MHC‐peptide complex with the T cell receptor. B cell presentation of mimicking foreign antigen to T cells is a possible mechanism for instigating an autoimmune response to self antigens that in turn can lead to autoimmune disease under particular conditions of antigen presentation, secondary signalling and effector cell repertoire. In this review evidence in support of epitope mimicry is examined in the light of the necessary immunological considerations of the theory.

Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain–Barré syndrome

“…If molecular mimicry by an infectious agent is the trigger of an autoimmune response leading to an autoimmune disease, several conditions must be satisfied: (i) the pathogen must be associated with the onset of the symptoms or disease in a convincing number of cases; (ii) a clinically detectable immune response to the pathogen must be demonstrable, at least at disease onset, which response must be shown to cross-react with host antigens of the affected tissues; and (iii) the pathology of the disease must be consistent with the immune response (13). As discussed below, these conditions have been established for GBS subsequent to C. jejuni infection, proof that GM1 mimicry by C. jejuni does cause GBS.…”

The pathogenesis of Chagas' disease: when autoimmune and parasite-specific immune responses meet

“…The main proposed mechanisms by which a microorganism could trigger an autoimmune disease are the sharing of epitopes (molecular mimicry) between the pathogen and the host, and the inflammation and tissue damage caused by the infection, leading to release self antigens, recruitment of inflammatory cells and/or production of immunomodulators and expression of surface molecules, which could, in concert, trigger or sustain an autoimmune response (Davies 1997, Fairweather et al 2001. One of the better characterized example of molecular mimicry between T. cruzi and a heart antigen was demonstrated by Cunha-Neto and co-workers.…”

Chagas' heart disease

“…However, the demonstration that this biological effect could have a clinical counterpart to support the autoimmune nature of this disease required the identification of an organ-specific autoantigen whose injection into the susceptible host could reproduce the lesion. Also, the myocardial damage in such circumstances, should be induced by passive transference of lymphocytes 151 .…”