Myelin oligodendrocyte glycoprotein has a dual role in T cell autoimmunity against central nervous system myelin

Hart, Bert A. ’t; Weissert, Robert

doi:10.1177/2055217316630999

Cited by 4 publications

(5 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 24 In another set of experiments in the same Biozzi mouse EAE model, we could show that EAE initiation can be achieved with MOG-deficient myelin, while the evolution of chronic relapsing disease is disturbed. 25 Combination of these findings underlies the concept that the activation of T cells against the immunogenic (read post-translationally modified 6 ) form of MOG occurs in the CNS draining lymphoid compartment.…”

Section: Eae In Marmosets: Pathogenic Mechanismsmentioning

confidence: 93%

See 1 more Smart Citation

An essential role of virus-infected B cells in the marmoset experimental autoimmune encephalomyelitis model

Hart

Kap

2017

Multiple Sclerosis Journal - Experimental, Translational and Cl

Self Cite

View full text Add to dashboard Cite

Infection with Epstein–Barr virus (EBV) has been associated with an enhanced risk of genetically susceptible individuals to develop multiple sclerosis (MS). However, an explanation for the contrast between the high EBV infection prevalence (60–90%) and the low MS prevalence (0.1%) eludes us. Here we propose a new concept for the EBV–MS association developed in the experimental autoimmune encephalomyelitis model in marmoset monkeys, which are naturally infected with the EBV-related γ1-herpesvirus CalHV3. The data indicate that the infection of B cells with a γ1-herpesvirus endows them with the capacity to activate auto-aggressive CD8+ T cells specific for myelin oligodendrocyte glycoprotein.

show abstract

Section: Eae In Marmosets: Pathogenic Mechanismsmentioning

confidence: 93%

“… 5 As reviewed elsewhere, evidence from marmoset EAE indicates that myelin oligodendrocyte glycoprotein (MOG) is the dominant trigger in CNS myelin for the development of chronic EAE. 6 …”

Section: Introductionmentioning

confidence: 99%

An essential role of virus-infected B cells in the marmoset experimental autoimmune encephalomyelitis model

Hart

Kap

2017

Multiple Sclerosis Journal - Experimental, Translational and Cl

Self Cite

View full text Add to dashboard Cite

show abstract

“…The minimal induction requirement is a peptide of 23 residues emulsified with mineral oil. The activation of this corepathogenic process appears to involve B cells infected with the EBV-related γ1-herpesvirus CalHV3 conditions present in MS lesions, makes MOG strongly immunogenic ('t Hart and Weissert 2016).…”

Section: Translational Relevance Of the Marmoset Eae Modelmentioning

confidence: 99%

An Unexpected Symbiosis of Animal Welfare and Clinical Relevance in a Refined Nonhuman Primate Model of Human Autoimmune Disease

Hart¹,

Laman²,

Kap³

2023

Nonhuman Primate Welfare

View full text Add to dashboard Cite

Aging Western populations are confronted with an increasing prevalence of chronic inflammatory and degenerative diseases for which adequate treatments are lacking. One of the major hurdles in therapy development is the poor translation of disease concepts, often developed in rodent disease models, into effective treatments for the patient. Reasons for the high failure rate of promising drug candidates are unforeseen toxicity and lack of efficacy. Essential elements of human disease are apparently lacking in the current preclinically used animal models. Results obtained in a generic nonhuman primate model of human autoimmunity, the marmoset experimental autoimmune encephalomyelitis (EAE) model, are discussed to emphasize the claim that primates are essential complementary models that can help to bridge the wide translational gap between mouse and man.

show abstract

“…14 As ligands of DC-SIGN are known to suppress maturation of dendritic cells to a full immunogenic state, we previously posited that MOG may have a role in the avoidance of autoreactive T-cell activation and neuroinflammation. 15,16…”

mentioning

confidence: 99%

“…The exact biological function of MOG is not known, but there is evidence that the N-linked glycan at position 31 interacts with the C-type lectin receptor DC-SIGN, which is expressed on microglial cells and on antigen-presenting cells within the brain-draining cervical lymph nodes (CLNs) . As ligands of DC-SIGN are known to suppress maturation of dendritic cells to a full immunogenic state, we previously posited that MOG may have a role in the avoidance of autoreactive T-cell activation and neuroinflammation. , …”

mentioning

confidence: 99%

Amyloid-like Behavior of Site-Specifically Citrullinated Myelin Oligodendrocyte Protein (MOG) Peptide Fragments inside EBV-Infected B-Cells Influences Their Cytotoxicity and Autoimmunogenicity

et al. 2018

View full text Add to dashboard Cite

Multiple sclerosis (MS) is an autoimmune disorder manifested via chronic inflammation, demyelination, and neurodegeneration inside the central nervous system. The progressive phase of MS is characterized by neurodegeneration, but unlike classical neurodegenerative diseases, amyloid-like aggregation of self-proteins has not been documented. There is evidence that citrullination protects an immunodominant peptide of human myelin oligodendrocyte glycoprotein (MOG34–56) against destructive processing in Epstein-Barr virus-infected B-lymphocytes (EBV-BLCs) in marmosets and causes exacerbation of ongoing MS-like encephalopathies in mice. Here we collected evidence that citrullination of MOG can also lead to amyloid-like behavior shifting the disease pathogenesis toward neurodegeneration. We observed that an immunodominant MOG peptide, MOG35–55, displays amyloid-like behavior upon site-specific citrullination at positions 41, 46, and/or 52. These amyloid aggregates are shown to be toxic to the EBV-BLCs and to dendritic cells at concentrations favored for antigen presentation, suggesting a role of amyloid-like aggregation in the pathogenesis of progressive MS.

show abstract

Myelin oligodendrocyte glycoprotein has a dual role in T cell autoimmunity against central nervous system myelin

Cited by 4 publications

References 24 publications

An essential role of virus-infected B cells in the marmoset experimental autoimmune encephalomyelitis model

An essential role of virus-infected B cells in the marmoset experimental autoimmune encephalomyelitis model

An Unexpected Symbiosis of Animal Welfare and Clinical Relevance in a Refined Nonhuman Primate Model of Human Autoimmune Disease

Amyloid-like Behavior of Site-Specifically Citrullinated Myelin Oligodendrocyte Protein (MOG) Peptide Fragments inside EBV-Infected B-Cells Influences Their Cytotoxicity and Autoimmunogenicity

Contact Info

Product

Resources

About