Molecular Mimicry

Abstract

Molecular mimicry is structural, functional or immunological similarities shared between macromolecules found on infectious pathogens and in host tissues. Molecular mimicry plays an important role in immune responses to infection and in autoimmune diseases. Infection may induce autoimmune responses which attack and destroy body tissues or organs. Normally, the body is tolerant to self‐antigens which are present in individual tissues. In autoimmune disease, tolerance is abrogated to self‐antigens, and tissues or organs are destroyed by the immune system. Molecular mimicry of a self‐antigen by an infectious pathogen, such as bacteria and viruses, may trigger autoimmune disease due to a crossreactive immune response against the infection. Crossreactive antigen–antibody and T cell–antigen reactions are used to identify the mimicking macromolecules on the pathogen and in tissues or organs. These parameters define the concept of molecular mimicry. Key Concepts: There are three types of mimicry. Immunological mimicry between dissimilar epitopes on chemically different molecules has changed the concept that an antibody molecule must recognize only a single antigenic epitope. Although molecular mimicry was once thought by immunologists to be a ‘phenomenon’ or ‘nonspecific immune reaction’, mimicry is now considered to be a part of the normal immune system and plays an important role in protection against pathogens. Microbial infections may activate the immune system and lead to a loss of immune tolerance which could allow expansion of high avidity crossreactive B‐ or T‐cell clones which through molecular mimicry may lead to autoimmune disease. Mimicry has been shown to lead to the induction of autoantibodies which alter signalling in cells.

Molecular mimicry: An explanation for autoimmune diseases and infertility

“…However, autoimmunity induced by molecular mimicry may occur when microbial and host antigens are similar, but differ enough to break self‐tolerance, which allowed mimicry to be classified into three broad categories viz. Type 1 with complete identity of amino acid sequences in different protein molecules; type 2 with structural similarities rather than amino acid sequence identities in the mimicking chemical structures; and lastly type 3 involving recognition of completely dissimilar chemical structures on separate molecules by a single antibody . Also of note is the fact that cross‐reactive Abs are not always entitled to diseased hosts only, in fact they might be present in normal individuals with increased Ab titre post‐infection, suggesting that besides mimicking epitopes, the development of autoimmune disease necessitates a susceptible host with pre‐disposing MHC haplotypes, elevated cytokine production or target organ sensitivity…”

The search for molecular mimicry in proteins carried by extracellular vesicles secreted by cells infected with Plasmodium falciparum

“…Another case of similarity could be obtained through convergent evolution, a phenomenon called consequential mimicry [11]. A typical example of this kind of event occurs when molecules -usually proteins, carbohydrates or deoxyribonucleic acid -shared between the pathogen and the host cause a cross-reaction in the presence of an active immune response [12].…”