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High immunogenicity of intracellular myelin oligodendrocyte glycoprotein epitopes.
J Immunol 2002; 169(1):548-56JI

Abstract

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the CNS with associated axonal loss. There is strong evidence for an autoimmune pathogenesis driven by myelin-specific T cells. Myelin oligodendrocyte glycoprotein (MOG) induces a type of experimental autoimmune encephalomyelitis in animals which is very MS-like since there are demyelinating CNS lesions and axonal loss. This underscores the potential role of MOG in MS pathogenesis. We performed a T cell reactivity pattern analysis of MS patients at the onset of relapse or progression of neurological deficits and controls that were stratified for the genetic risk factor HLA-DRB1*1501. For the first time, we show that there is an HLA-DR-restricted promiscuous dominant epitope for CD4(+) T cells within the transmembrane/intracellular part of MOG comprising aa 146-154 (FLCLQYRLR). Surprisingly, controls had broader T cell reactivity patterns toward MOG peptides compared with MS patients, and the transmembrane and intracellular parts of MOG were much more immunogenic compared with the extracellular part. Measurements of in vitro binding affinities revealed that HLA-DRB1*1501 molecules bound MOG 146-154 with intermediate and HLA-DRB1*0401 molecules with weak affinities. The binding of MOG 146-154 was comparable or better than myelin basic protein 85-99, which is the dominant myelin basic protein epitope in context with HLA-DRB1*1501 molecules in MS patients. This is the first study in which the data underscore the need to investigate the pathogenic or regulatory role of the transmembrane and intracellular part of MOG for MS in more detail.

Authors+Show Affiliations

Department of Neurology, University of Tübingen, Tübingen, Germany. robert.weissert@uni-tuebingen.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12077287

Citation

Weissert, Robert, et al. "High Immunogenicity of Intracellular Myelin Oligodendrocyte Glycoprotein Epitopes." Journal of Immunology (Baltimore, Md. : 1950), vol. 169, no. 1, 2002, pp. 548-56.
Weissert R, Kuhle J, de Graaf KL, et al. High immunogenicity of intracellular myelin oligodendrocyte glycoprotein epitopes. J Immunol. 2002;169(1):548-56.
Weissert, R., Kuhle, J., de Graaf, K. L., Wienhold, W., Herrmann, M. M., Müller, C., ... Melms, A. (2002). High immunogenicity of intracellular myelin oligodendrocyte glycoprotein epitopes. Journal of Immunology (Baltimore, Md. : 1950), 169(1), pp. 548-56.
Weissert R, et al. High Immunogenicity of Intracellular Myelin Oligodendrocyte Glycoprotein Epitopes. J Immunol. 2002 Jul 1;169(1):548-56. PubMed PMID: 12077287.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High immunogenicity of intracellular myelin oligodendrocyte glycoprotein epitopes. AU - Weissert,Robert, AU - Kuhle,Jens, AU - de Graaf,Katrien L, AU - Wienhold,Wolfgang, AU - Herrmann,Martin M, AU - Müller,Claudia, AU - Forsthuber,Thomas G, AU - Wiesmüller,Karl-Heinz, AU - Melms,Arthur, PY - 2002/6/22/pubmed PY - 2002/8/14/medline PY - 2002/6/22/entrez SP - 548 EP - 56 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 169 IS - 1 N2 - Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the CNS with associated axonal loss. There is strong evidence for an autoimmune pathogenesis driven by myelin-specific T cells. Myelin oligodendrocyte glycoprotein (MOG) induces a type of experimental autoimmune encephalomyelitis in animals which is very MS-like since there are demyelinating CNS lesions and axonal loss. This underscores the potential role of MOG in MS pathogenesis. We performed a T cell reactivity pattern analysis of MS patients at the onset of relapse or progression of neurological deficits and controls that were stratified for the genetic risk factor HLA-DRB1*1501. For the first time, we show that there is an HLA-DR-restricted promiscuous dominant epitope for CD4(+) T cells within the transmembrane/intracellular part of MOG comprising aa 146-154 (FLCLQYRLR). Surprisingly, controls had broader T cell reactivity patterns toward MOG peptides compared with MS patients, and the transmembrane and intracellular parts of MOG were much more immunogenic compared with the extracellular part. Measurements of in vitro binding affinities revealed that HLA-DRB1*1501 molecules bound MOG 146-154 with intermediate and HLA-DRB1*0401 molecules with weak affinities. The binding of MOG 146-154 was comparable or better than myelin basic protein 85-99, which is the dominant myelin basic protein epitope in context with HLA-DRB1*1501 molecules in MS patients. This is the first study in which the data underscore the need to investigate the pathogenic or regulatory role of the transmembrane and intracellular part of MOG for MS in more detail. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/12077287/High_immunogenicity_of_intracellular_myelin_oligodendrocyte_glycoprotein_epitopes_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=12077287 DB - PRIME DP - Unbound Medicine ER -