Disease relevance of Molecular Mimicry

• A panel of 129 peptides that matched the molecular mimicry motif was tested on seven MBP-specific T cell clones from multiple sclerosis patients [1].
• As a model for molecular mimicry, we studied patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease that can be indistinguishable from MS (refs. 5,6,7) [2].
• To study the potential of virus-induced molecular mimicry to initiate autoimmune demyelination, a nonpathogenic TMEV variant was engineered to encode a 30-mer peptide encompassing the immunodominant encephalitogenic myelin proteolipid protein (PLP139-151) epitope [3].
• BACKGROUND & AIMS: The mechanism for development of primary biliary cirrhosis (PBC) remains enigmatic, but molecular mimicry has been implicated because of well-known cross-reactivity of human mitochondrial autoantigens and equivalent bacterial antigens [4].
• The molecular mimicry between gp120 and rabies virus glycoprotein is confirmed by cross-reacting antibodies [5].

High impact information on Molecular Mimicry

• Molecular mimicry in development: identification of ste11+ as a substrate and mei3+ as a pseudosubstrate inhibitor of ran1+ kinase [6].
• Because ligation of CD44 by hyaluronic acid can induce epithelial cell movement on extracellular matrix, we investigated whether molecular mimicry by the GAS hyaluronic acid capsule might induce similar cellular responses [7].
• Molecular mimicry mediated by MHC class Ib molecules after infection with gram-negative pathogens [8].
• In an unusual example of molecular mimicry, a negatively charged surface on this alpha-helix, by imitating single-stranded DNA, interacts with the loop L2 homologous pairing region of RecA and interferes with the activation of RecA [9].
• Sialic acid is, therefore, a host molecule to be copied (molecular mimicry), eaten (nutrition), and interpreted (cell signaling) by diverse metabolic machinery in all major groups of mammalian pathogens and commensals [10].

Chemical compound and disease context of Molecular Mimicry

• Toward a better understanding of the basis of the molecular mimicry of polysaccharide antigens by peptides: the example of Shigella flexneri 5a [11].
• Amino acid homology, as well as cysteine pairing similar to the laminin gamma1 chain epidermal growth factor-like repeat 11, suggests conformational similarity between the two molecules and raises the possibility of molecular mimicry in the pathogenesis of Graves' disease [12].
• Both H3-10A1 and CVB3W have cross-reactive epitopes between the adenine translocator protein and the virion which are indicative of antigenic mimicry and may be the basis for the autoimmunity to cardiac antigens [13].
• In other neurological disease, some etiologic factors have been detected as in the case of Guillain-Barrè syndrome in which molecular mimicry between Campylobacter jejuni endotoxin and GM1 ganglioside may cause an acute inflammatory polyneuropathy [14].
• Here we report findings about the existence of a mechanism of functional molecular mimicry which could enable the binding of HIV-1 gp120 to nicotinic acetylcholine receptors in muscle cells and neurons [15].

Biological context of Molecular Mimicry

• Sequence homology of the diabetes-associated autoantigen glutamate decarboxylase with coxsackie B4-2C protein and heat shock protein 60 mediates no molecular mimicry of autoantibodies [16].
• Ankylosing spondylitis, immune-response-genes and molecular mimicry [17].
• Single-stranded DNA mimicry in the p53 transactivation domain interaction with replication protein A [18].
• An apparent dimerization motif in the third domain of alpha-fetoprotein: molecular mimicry of the steroid/thyroid nuclear receptor superfamily [19].
• Thus a virus infection can activate an immune response against a specific autoantigen, providing possibilities for destruction of non-infected host cells, as originally proposed by Fujinami & Oldstone (1985), and also for the molecular mimicry model for induction of autoimmunity [20].

Anatomical context of Molecular Mimicry

• The E. histolytica adhesin shared sequence similarities and antigenic cross-reactivity with CD59, a membrane inhibitor of C5b-9 in human blood cells, suggesting both molecular mimicry and shared complement-inhibitory functions [21].
• To investigate the molecular basis of antigenic mimicry by peptides, we studied a panel of closely related mAbs directed against the cell-wall polysaccharide of group A Streptococcus [22].
• The possible relevance of molecular mimicry between a human coronavirus and the myelin basic protein component of myelin in the generation of this autoimmune reaction was evaluated [23].
• Cross-reactivity due to molecular mimicry at the B-cell level was shown between the CYP2D6 and the HCV NS3 and NS5a proteins and could explain the presence of anti-LKM1 in patients chronically infected with HCV [24].
• Finally we discuss viral mechanisms for sabotaging or manipulating the chemokine system, in part to illustrate the level of molecular mimicry that viruses have achieved and the evolutionary pressure imposed on the immune system by these pathogens [25].

Associations of Molecular Mimicry with chemical compounds

• The structure of one such cationic molecule suggested a molecular mimicry with spermine, a ubiquitous endogenous biogenic amine that increases significantly at sites of inflammation and infection [26].
• For an epitope that is sequence-specific (anti-FIPV system), molecular mimicry appears to be present as evidenced by the sequence homology between the CDR loops of the anti-id and the epitope of the original antigen [27].
• This unique molecular mimicry has provided clues leading to the discovery of guanylin and insight into the mechanism of action of these intestinal peptides [28].
• Comparison of this structure with that of ConA bound to methyl alpha-d-mannopyranoside provided direct structural evidence of molecular mimicry in the context of ligand receptor binding [29].
• Mercuric conjugates of cysteine are transported by the amino acid transporter system b(0,+): implications of molecular mimicry [30].

Gene context of Molecular Mimicry

• Thus, unlike Wnt antagonists, which exert their effects by molecular mimicry of Fz or Wnt sequestration through other mechanisms, Dkk-1 specifically inhibits canonical Wnt signalling by binding to the LRP6 component of the receptor complex [31].
• Molecular mimicry between HCV proteins and CYP2D6 has been proposed to explain the emergence of these autoantibodies [24].
• This suggested that US28 was originally copied from a human chemokine receptor gene, perhaps to provide the virus with a selective advantage through molecular mimicry [32].
• The antigenic epitopes of NT-modified enolase and Hspa5 exhibited sequence homology and cross-reactivity, suggesting that epitope spreading may occur through a molecular mimicry mechanism [33].
• Transport of a neurotoxicant by molecular mimicry: the methylmercury-L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2 [34].

Analytical, diagnostic and therapeutic context of Molecular Mimicry

• Although the exact molecular mimicry relationship of this 180-186 epitope with the proteoglycan moiety of cartilage remains to be elucidated, the crucial significance of hsp65 immunity has been substantiated further, not only in adjuvant arthritis, but also in other models of experimentally induced arthritis [35].

References