Molecular mimicry between a viral peptide and a myelin oligodendrocyte glycoprotein peptide induces autoimmune demyelinating disease in mice

Mokhtarian, Foroozan; Zhang, Zhiguang; Shi, Yong; Gonzales, Efrain; Sobel, Raymond A.

doi:10.1016/s0165-5728(98)00254-9

Cited by 102 publications

(76 citation statements)

References 35 publications

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“…Molecular mimicry is a natural phenomenon and several examples exist to provide a proof of concept that the microbial mimics can break self-tolerance and induce autoimmune responses in various animal studies, including experimental autoimmune encephalomyelitis (EAE), the disease model for MS in humans (Fujinami et al, 2006;Gautam et al, 1998;Mokhtarian et al, 1999). EAE can be induced by active immunization with emulsions containing myelin antigens in complete Freund's adjuvant (CFA) or by adoptively transferring myelin antigen (Ag)-specific T cells into the susceptible animals (Tuohy et al, 1989;Whitham et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

“…The microbial mimics capable of inducing EAE have been reported for all the above except for PLP. These include Herpes virus saimiri (Gautam et al, 1998), Hepatitis B virus (Fujinami and Oldstone, 1985), JC virus (Mao et al, 2007), Chlamydia pneumoniae (Conant and Swanborg, 2003), Papilloma virus (MBP mimics) (Ruiz et al, 1999), and Semliki forest virus (MOG mimic) (Mokhtarian et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

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An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice

Massilamany

Steffen

Reddy

2010

Journal of Neuroimmunology

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Epitope from Acanthamoeba castellanii That Cross-React with Proteolipid Protein 139-151-Reactive T Cells Induces Autoimmune Encephalomyelitis in SJL Mice" (2010). Jay Reddy Publications. 17. https://digitalcommons.unl.edu/vbsjayreddy/17 tein databases. This search resulted in the identification of one novel peptide spanning aa 83-95 of rhodanese-related sulfurtransferase in Acanthamoeba castellanii (ACA) and it induces EAE similar to that of PLP 139-151. Materials and methods MiceFour to six-week-old female SJL/J (H-2 s ) mice were obtained from the Jackson Laboratory (Bar Harbor, Maine). The mice were maintained in accordance with the animal protocol guidelines of the University of Nebraska-Lincoln, Lincoln, Nebraska. Peptide synthesis and immunization proceduresPLP 139-151 (HSLGKWLGHPDKF), ACA 83-95 (YFLLKWLGH-PNVS) and neuraminidase (NASE) 101-120 (EALVRQGLAKVAY-VYKPNNT) were synthesized on 9-fluorenylmethyloxycarbonyl chemistry (Neopeptide, Cambridge, Massachusetts). All peptides were HPLC-purified (N90%) and confirmed by mass spectroscopy. To measure recall responses 100 µg of each peptide emulsified in CFA was administered subcutaneously in the flank. For disease induction, Mycobacterium tuberculosis (MTB) H37RA extract (Difco Laboratories, Detroit, Michigan) was added as an additional component to a final concentration of 5 mg/ml. Pertussis toxin (List Biological Laboratories, Campbell, California) was administered (100 ng per mouse) intraperitoneally on day 0 and day 2 postimmunization. Identification of microbial peptides that mimic PLP 139-151PLP 139-151 is an immunodominant epitope in which the critical residues required for major histocompatibility complex (MHC) class II and T cell receptor (TCR)-binding have been well-characterized (Figure 1). By using PLP 139-151 as a putative antigen, we performed pattern search using the prosite scan of the Bioinformatics Toolkit

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice

Massilamany

Steffen

Reddy

2010

Journal of Neuroimmunology

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“…One mechanism discussed in this context is molecular mimicry (3); the induction of autoimmunity due to the presence of shared sequence or structural homologies with a foreign Ag (4). Many peptides derived from common viruses share linear sequence homologies with myelin proteins, and in animal models these can induce cross-reactive and potentially pathogenic T cell responses (5)(6)(7)(8)(9)(10). This cross-reactive response reflects the degeneracy of peptide-MHC complex recognition by the TCR, which allows a single receptor to bind a hierarchy of peptide ligands (6,11).…”

mentioning

confidence: 99%

“…However, if MOG is expressed in immune organs, recent studies using genetically manipulated MOG-deficient mice demonstrate that MOG itself is unable to induce immunological selftolerance (39). As a consequence, potentially pathogenic MOGreactive lymphocytes are retained within the healthy immune repertoire and may be activated due to mimicry with epitopes derived from environmental agents (8,19,40). In the case of BTN, immunization in CFA activates a cross-reactive Th1 CD4 ϩ T cell response to MOG that initiates a subclinical encephalomyelitis (19).…”

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confidence: 99%

Antibody Cross-Reactivity between Myelin Oligodendrocyte Glycoprotein and the Milk Protein Butyrophilin in Multiple Sclerosis

Guggenmos

Schubart

Ogg

et al. 2004

The Journal of Immunology

119

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The etiology of multiple sclerosis (MS) is believed to involve environmental factors, but their identity and mode of action are unknown. In this study, we demonstrate that Ab specific for the extracellular Ig-like domain of myelin oligodendrocyte glycoprotein (MOG) cross-reacts with a homologous N-terminal domain of the bovine milk protein butyrophilin (BTN). Analysis of paired samples of MS sera and cerebrospinal fluid (CSF) identified a BTN-specific Ab response in the CNS that differed in its epitope specificity from that in the periphery. This effect was statistically significant for the Ab response to BTN76–100 (p = 0.0026), which cosequestered in the CSF compartment with Ab to the homologous MOG peptide MOG76–100 in 34% of MS patients (n = 35). These observations suggested that intratheccal synthesis of Ab recognizing BTN peptide epitopes in the CNS was sustained by molecular mimicry with MOG. Formal evidence of molecular mimicry between the two proteins was obtained by analyzing MOG-specific autoantibodies immunopurified from MS sera. The MOG-specific Ab repertoire cross-reacts with multiple BTN peptide epitopes including a MOG/BTN76–100-specific component that occurred at a higher frequency in MS patients than in seropositive healthy controls, as well as responses to epitopes within MOG/BTN1–39 that occur at similar frequencies in both groups. The demonstration of molecular mimicry between MOG and BTN, along with sequestration of BTN-reactive Ab in CSF suggests that exposure to this common dietary Ag may influence the composition and function of the MOG-specific autoimmune repertoire during the course of MS.

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“…MOG is also a potent candidate autoantigen in MS, since it has several properties typical for autoantigens like (a) molecular mimicry, that is, sharing of epitopes with common infectious agents, 20 (b) determinant spreading 21 and (c) complement binding. 22 Non-MHC consensus From 295 consensus genes, 214 are located outside of the MHC locus.…”

Section: Mhc Consensusmentioning

confidence: 99%

Intergenomic consensus in multifactorial inheritance loci: the case of multiple sclerosis

Serrano-Fernández

Ibrahim

et al. 2004

Genes Immun

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Genetic linkage and association studies define chromosomal regions, quantitative trait loci (QTLs), which influence the phenotype of polygenic diseases. Here, we describe a global approach to determine intergenomic consensus of those regions in order to fine map QTLs and select particularly promising candidate genes for disease susceptibility or other polygenic traits. Exemplarily, human multiple sclerosis (MS) susceptibility regions were compared for sequence similarity with mouse and rat QTLs in its animal model experimental allergic encephalomyelitis (EAE). The number of intergenomic MS/EAE consensus genes (295) is significantly higher than expected if the animal model was unrelated to the human disease. Hence, this approach contributes to the empirical evaluation of animal models for their applicability to the study of human diseases.

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Molecular mimicry between a viral peptide and a myelin oligodendrocyte glycoprotein peptide induces autoimmune demyelinating disease in mice

Cited by 102 publications

References 35 publications

An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice

An epitope from Acanthamoeba castellanii that cross-react with proteolipid protein 139-151-reactive T cells induces autoimmune encephalomyelitis in SJL mice

Antibody Cross-Reactivity between Myelin Oligodendrocyte Glycoprotein and the Milk Protein Butyrophilin in Multiple Sclerosis

Intergenomic consensus in multifactorial inheritance loci: the case of multiple sclerosis

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