Molecular Mimicry as a Mechanism of Autoimmune Disease

Abstract

A variety of mechanisms have been suggested as the means by which infections can initiate and/or exacerbate autoimmune diseases. One mechanism is molecular mimicry, where a foreign antigen shares sequence or structural similarities with self-antigens. Molecular mimicry has typically been characterized on an antibody or T cell level. However, structural relatedness between pathogen and self does not account for T cell activation in a number of autoimmune diseases. A proposed mechanism that could have been misinterpreted for molecular mimicry is the expression of dual T cell receptors (TCR) on a single T cell. These T cells have dual reactivity to both foreign and self-antigens leaving the host vulnerable to foreign insults capable of triggering an autoimmune response. In this review, we briefly discuss what is known about molecular mimicry followed by a discussion of the current understanding of dual TCRs. Finally, we discuss three mechanisms, including molecular mimicry, dual TCRs and chimeric TCRs, by which dual reactivity of the T cell may play a role in autoimmune diseases.

Specific antigen(s) in sarcoidosis: a link to autoimmunity?

“…that vimentin resembles the molecular structure of a microbial antigen ( possibly mKatG) and reactive T-cells might cross-react to a vimentin self antigen. In fact, molecular mimicry indeed plays a role in several autoimmune or autoaggressive diseases [20]. Thus, the work presented here might give an explanation why we do see reactivity against bacterial antigens despite the fact that these microorganisms are no longer present.…”

T cell epitope redundancy: cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity

“…Human commensal pathogens that have established a pattern of 'hit and stay' (such as herpes simplex virus) have more redundant sequences than pathogens that 'hit and run' (such as Ebola and Marburg) [17,18]. To what degree this redundancy may contribute to autoimmunity, is as yet unknown [19].…”

Molecular mimicry of MAGE-A6 andMycoplasma penetransHF-2 epitopes in the induction of antitumor CD8+T-cell responses

“…24,25 Viral myocarditis, Lyme disease, rheumatoid arthritis, multiple sclerosis, and virus-induced autoimmune diabetes are autoimmune diseases that are considered to be initiated or aggravated by immune challenge with microbial pathogens. [24][25][26][27][28] Consistent with this model, we have previously shown that a MAGE-A6-derived peptide, MAGE-A6 172-187 , and a peptide derived from the permease protein of the ubiquitous Mycoplasma penetrans HF-2 bacterium (HF-2 216-229 ) share a high-degree of structural homology and immunologic cross-reactivity in the CD4 C T-cell compartment present in a broad range of healthy donors and melanoma patients. 29 We now show that these same MAGE-A6 172-187 and HF-2 216-229 peptides can induce a cross-reactive, polyclonal CD8 C T-cell repertoire in HLA-A*0201 (HLA-A2)…”