Genetic variation in myelin oligodendrocyte glycoprotein expression and susceptibility to experimental autoimmune encephalomyelitis

Pagany, Maria; Jagodic, Maja; Bourquin, Carole; Olsson, Tomas; Linington, Christopher

doi:10.1016/s0165-5728(03)00124-3

Cited by 21 publications

(19 citation statements)

References 29 publications

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“…The lack of reactivation coincided with a lack of long-term contacts with local antigen-presenting phagocytes. We suspect that this truncated response reflects decreased availability of MOG autoantigen in the Lewis rat, involving decreased local production (23) and/or suboptimal binding of MOG epitopes to relevant MHC class II molecules (24).…”

Section: Establishment Of Gfp-labeled Antigen-specific T Cell Linesmentioning

confidence: 99%

2-photon imaging of phagocyte-mediated T cell activation in the CNS

Pesic

Bartholomäus

Kyratsous³

et al. 2013

J. Clin. Invest.

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Autoreactive T cells can infiltrate the CNS to cause disorders such as multiple sclerosis. In order to visualize T cell activation in the CNS, we introduced a truncated fluorescent derivative of nuclear factor of activated T cells (NFAT) as a real-time T cell activation indicator. In experimental autoimmune encephalomyelitis, a rat model of multiple sclerosis, we tracked T cells interacting with structures of the vascular blood-brain barrier (BBB). 2-photon imaging documented the cytoplasmic-nuclear translocation of fluorescent NFAT, indicative of calcium-dependent activation of the T cells in the perivascular space, but not within the vascular lumen. The activation was related to contacts with the local antigen-presenting phagocytes and was noted only in T cells with a high pathogenic potential. T cell activation implied the presentation of an autoantigen, as the weakly pathogenic T cells, which remained silent in the untreated hosts, were activated upon instillation of exogenous autoantigen. Activation did not cogently signal long-lasting arrest, as individual T cells were able to sequentially contact fresh APCs. We propose that the presentation of local autoantigen by BBB-associated APCs provides stimuli that guide autoimmune T cells to the CNS destination, enabling them to attack the target tissue.

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Section: Establishment Of Gfp-labeled Antigen-specific T Cell Linesmentioning

confidence: 99%

2-photon imaging of phagocyte-mediated T cell activation in the CNS

Pesic

Bartholomäus

Kyratsous³

et al. 2013

J. Clin. Invest.

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“…Immunizing Lewis rats with murine MOG and CFA causes a rather mild form of EAE, characterized by occasional focal demyelination with only small numbers of T cells in the CNS, suggesting that MOG is a poor encephalitogen in the Lewis rat [Adelmann et al 1995]. It has been proposed that this difference is due to higher expression of MOG in the CNS of BN rats compared with Lewis rats and that this increase in protein expression is caused by polymorphisms in the non-coding region of the MOG gene [Pagany et al 2003]. …”

Section: Historically: Why Is Mog Interesting As a Target?mentioning

confidence: 99%

Glycoproteins as targets of autoantibodies in CNS inflammation: MOG and more

Mayer

Meinl

2012

Ther Adv Neurol Disord

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Lessons from animal models MOG can be involved in CNS autoimmunity in principally two different ways. First, MOGspecific T cells evoke CNS inflammation. Second, anti-MOG antibodies lead to the induction of demyelination. Demyelination is a characteristic feature of MS lesions indicated by the presence of naked demyelinated axons. Glycoproteins as targets of autoantibodies in CNS inflammation: MOG and more Marie Cathrin Mayer and Edgar MeinlAbstract: B cells and antibodies constitute an important element in different inflammatory diseases of the central nervous system (CNS). Autoantibodies can serve as a biomarker to identify disease subgroups and may in addition contribute to the pathogenic process. One candidate autoantigen for multiple sclerosis (MS) is myelin oligodendrocyte glycoprotein (MOG). MOG is localized at the outermost surface of myelin in the CNS and has been the focus of extensive research for more than 30 years. Its role as an important autoantigen for T cells and as a target of demyelinating autoantibodies has been established in several variants of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The literature regarding antibodies to MOG in MS patients is confusing and contradictory. Recent studies, however, have described high levels of antibodies to conformationally correct MOG in pediatric acquired demyelination, both acute disseminated encephalomyelitis (ADEM) and MS. In adult MS, such antibodies are rarely found and then only at low levels. In this review, we summarize key findings from animal models and patient studies, discuss challenges in detecting anti-MOG antibodies in patients and present recent approaches to identifying new autoantigens in MS.

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“…Susceptibility has been attributed to the class II region and to the telomeric class I region as well (Weissert et al 1998;Stefferl et al 1999). Interestingly, Mog maps to the telomeric end of the MHC, and the highly susceptible BN rat exhibits a stronger expression of the MOG protein compared to less susceptible strains (Pagany et al 2003). The rat RT1 n haplotype sequence generated by us can now be used to study the molecular basis of MHC-controlled disease traits and serve as a reference sequence.…”

Section: Rat Mhc and Disease Associationmentioning

confidence: 99%

The Genomic Sequence and Comparative Analysis of the Rat Major Histocompatibility Complex

Hurt¹,

Walter²,

Sudbrak³

et al. 2004

Genome Res.

114

106

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We have determined the sequence of a 4-Mb interval on rat chromosome 20p12 that encompasses the rat major histocompatibility complex (MHC). This is the first report of a finished sequence for a segment of the rat genome and constitutes one of the largest contiguous sequences thus far for rodent genomes in general. The rat MHC is, next to the human MHC, the second mammalian MHC sequenced to completion. Our analysis has resulted in the identification of at least 220 genes located within the sequenced interval. Although gene content and order are well conserved in the class II and class III gene intervals as well as the framework gene regions, profound rat-specific features were encountered within the class I gene regions, in comparison to human and mouse. Class I region-associated differences were found both at the structural level, the number, and organization of class I genes and gene families, and, in a more global context, in the way that evolution worked to shape the present-day rat MHC.

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Genetic variation in myelin oligodendrocyte glycoprotein expression and susceptibility to experimental autoimmune encephalomyelitis

Cited by 21 publications

References 29 publications

2-photon imaging of phagocyte-mediated T cell activation in the CNS

2-photon imaging of phagocyte-mediated T cell activation in the CNS

Glycoproteins as targets of autoantibodies in CNS inflammation: MOG and more

The Genomic Sequence and Comparative Analysis of the Rat Major Histocompatibility Complex

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