Tags

Type your tag names separated by a space and hit enter

The myelin-associated oligodendrocytic basic protein region MOBP15-36 encompasses the immunodominant major encephalitogenic epitope(s) for SJL/J mice and predicted epitope(s) for multiple sclerosis-associated HLA-DRB1*1501.
J Immunol 2004; 173(2):1426-35JI

Abstract

Autoimmune response to the myelin-associated oligodendrocytic basic protein (MOBP), a CNS-specific myelin constituent, was recently suggested to play a role in the pathogenesis of multiple sclerosis (MS). The pathogenic autoimmune response to MOBP and the associated pathology in the CNS have not yet been fully investigated. In this study, we have characterized the clinical manifestations, pathology, T cell epitope-specificity, and TCRs associated with experimental autoimmune encephalomyelitis (EAE) induced in SJL/J mice with recombinant mouse MOBP (long isoform, 170 aa). Analysis of encephalitogenic MOBP-reactive T cells for reactivity to overlapping MOBP peptides defined MOBP15-36 as their major immunodominant epitope. Accordingly, MOBP15-36 was demonstrated to be the major encephalitogenic MOBP epitope for SJL/J mice, inducing severe/chronic clinical EAE associated with intense perivascular and parenchymal infiltrations, widespread demyelination, axonal loss, and remarkable optic neuritis. Molecular modeling of the interaction of I-A(s) with MOBP15-36, together with analysis of the MOBP15-36-specific T cell response to truncated peptides, suggests MOBP20-28 as the core sequence for I-A(s)-restricted recognition of the encephalitogenic region MOBP15-36. Although highly focused in their epitope specificity, the encephalitogenic MOBP-reactive T cells displayed a widespread usage of TCR Vbeta genes. These results would therefore favor epitope-directed, rather than TCR-targeted, approaches to therapy of MOBP-associated pathogenic autoimmunity. Localization by molecular modeling of a potential HLA-DRB1*1501-associated MOBP epitope within the encephalitogenic MOBP15-36 sequence suggests the potential relevance of T cell reactivity against MOBP15-36 to MS. The reactivity to MOBP15-36 detected in MS shown here and in another study further emphasizes the potential significance of this epitope for MS.

Authors+Show Affiliations

Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.No 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

15240739

Citation

de Rosbo, Nicole Kerlero, et al. "The Myelin-associated Oligodendrocytic Basic Protein Region MOBP15-36 Encompasses the Immunodominant Major Encephalitogenic Epitope(s) for SJL/J Mice and Predicted Epitope(s) for Multiple Sclerosis-associated HLA-DRB1*1501." Journal of Immunology (Baltimore, Md. : 1950), vol. 173, no. 2, 2004, pp. 1426-35.
de Rosbo NK, Kaye JF, Eisenstein M, et al. The myelin-associated oligodendrocytic basic protein region MOBP15-36 encompasses the immunodominant major encephalitogenic epitope(s) for SJL/J mice and predicted epitope(s) for multiple sclerosis-associated HLA-DRB1*1501. J Immunol. 2004;173(2):1426-35.
de Rosbo, N. K., Kaye, J. F., Eisenstein, M., Mendel, I., Hoeftberger, R., Lassmann, H., ... Ben-Nun, A. (2004). The myelin-associated oligodendrocytic basic protein region MOBP15-36 encompasses the immunodominant major encephalitogenic epitope(s) for SJL/J mice and predicted epitope(s) for multiple sclerosis-associated HLA-DRB1*1501. Journal of Immunology (Baltimore, Md. : 1950), 173(2), pp. 1426-35.
de Rosbo NK, et al. The Myelin-associated Oligodendrocytic Basic Protein Region MOBP15-36 Encompasses the Immunodominant Major Encephalitogenic Epitope(s) for SJL/J Mice and Predicted Epitope(s) for Multiple Sclerosis-associated HLA-DRB1*1501. J Immunol. 2004 Jul 15;173(2):1426-35. PubMed PMID: 15240739.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The myelin-associated oligodendrocytic basic protein region MOBP15-36 encompasses the immunodominant major encephalitogenic epitope(s) for SJL/J mice and predicted epitope(s) for multiple sclerosis-associated HLA-DRB1*1501. AU - de Rosbo,Nicole Kerlero, AU - Kaye,Joel F, AU - Eisenstein,Miriam, AU - Mendel,Itzhack, AU - Hoeftberger,Romana, AU - Lassmann,Hans, AU - Milo,Roni, AU - Ben-Nun,Avraham, PY - 2004/7/9/pubmed PY - 2004/8/28/medline PY - 2004/7/9/entrez SP - 1426 EP - 35 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 173 IS - 2 N2 - Autoimmune response to the myelin-associated oligodendrocytic basic protein (MOBP), a CNS-specific myelin constituent, was recently suggested to play a role in the pathogenesis of multiple sclerosis (MS). The pathogenic autoimmune response to MOBP and the associated pathology in the CNS have not yet been fully investigated. In this study, we have characterized the clinical manifestations, pathology, T cell epitope-specificity, and TCRs associated with experimental autoimmune encephalomyelitis (EAE) induced in SJL/J mice with recombinant mouse MOBP (long isoform, 170 aa). Analysis of encephalitogenic MOBP-reactive T cells for reactivity to overlapping MOBP peptides defined MOBP15-36 as their major immunodominant epitope. Accordingly, MOBP15-36 was demonstrated to be the major encephalitogenic MOBP epitope for SJL/J mice, inducing severe/chronic clinical EAE associated with intense perivascular and parenchymal infiltrations, widespread demyelination, axonal loss, and remarkable optic neuritis. Molecular modeling of the interaction of I-A(s) with MOBP15-36, together with analysis of the MOBP15-36-specific T cell response to truncated peptides, suggests MOBP20-28 as the core sequence for I-A(s)-restricted recognition of the encephalitogenic region MOBP15-36. Although highly focused in their epitope specificity, the encephalitogenic MOBP-reactive T cells displayed a widespread usage of TCR Vbeta genes. These results would therefore favor epitope-directed, rather than TCR-targeted, approaches to therapy of MOBP-associated pathogenic autoimmunity. Localization by molecular modeling of a potential HLA-DRB1*1501-associated MOBP epitope within the encephalitogenic MOBP15-36 sequence suggests the potential relevance of T cell reactivity against MOBP15-36 to MS. The reactivity to MOBP15-36 detected in MS shown here and in another study further emphasizes the potential significance of this epitope for MS. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/15240739/The_myelin_associated_oligodendrocytic_basic_protein_region_MOBP15_36_encompasses_the_immunodominant_major_encephalitogenic_epitope_s__for_SJL/J_mice_and_predicted_epitope_s__for_multiple_sclerosis_associated_HLA_DRB1_1501_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=15240739 DB - PRIME DP - Unbound Medicine ER -