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T cell epitopes of human myelin oligodendrocyte glycoprotein identified in HLA-DR4 (DRB1*0401) transgenic mice are encephalitogenic and are presented by human B cells.
J Immunol 2001; 167(12):7119-25JI

Abstract

Myelin oligodendrocyte glycoprotein (MOG) is an Ag present in the myelin sheath of the CNS thought to be targeted by the autoimmune T cell response in multiple sclerosis (MS). In this study, we have for the first time characterized the T cell epitopes of human MOG restricted by HLA-DR4 (DRB1*0401), an MHC class II allele associated with MS in a subpopulation of patients. Using MHC binding algorithms, we have predicted MOG peptide binding to HLA-DR4 (DRB1*0401) and subsequently defined the in vivo T cell reactivity to overlapping MOG peptides by testing HLA-DR4 (DRB1*0401) transgenic mice immunized with recombinant human (rh)MOG. The data indicated that MOG peptide 97-108 (core 99-107, FFRDHSYQE) was the immunodominant HLA-DR4-restricted T cell epitope in vivo. This peptide has a high in vitro binding affinity for HLA-DR4 (DRB1*0401) and upon immunization induced severe experimental autoimmune encephalomyelitis in the HLA-DR4 transgenic mice. Interestingly, the same peptide was presented by human B cells expressing HLA-DR4 (DRB1*0401), suggesting a role for the identified MOG epitopes in the pathogenesis of human MS.

Authors+Show Affiliations

Institute of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. tgf2@pop.cwru.eduNo affiliation info availableNo 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
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11739534

Citation

Forsthuber, T G., et al. "T Cell Epitopes of Human Myelin Oligodendrocyte Glycoprotein Identified in HLA-DR4 (DRB1*0401) Transgenic Mice Are Encephalitogenic and Are Presented By Human B Cells." Journal of Immunology (Baltimore, Md. : 1950), vol. 167, no. 12, 2001, pp. 7119-25.
Forsthuber TG, Shive CL, Wienhold W, et al. T cell epitopes of human myelin oligodendrocyte glycoprotein identified in HLA-DR4 (DRB1*0401) transgenic mice are encephalitogenic and are presented by human B cells. J Immunol. 2001;167(12):7119-25.
Forsthuber, T. G., Shive, C. L., Wienhold, W., de Graaf, K., Spack, E. G., Sublett, R., ... Weissert, R. (2001). T cell epitopes of human myelin oligodendrocyte glycoprotein identified in HLA-DR4 (DRB1*0401) transgenic mice are encephalitogenic and are presented by human B cells. Journal of Immunology (Baltimore, Md. : 1950), 167(12), pp. 7119-25.
Forsthuber TG, et al. T Cell Epitopes of Human Myelin Oligodendrocyte Glycoprotein Identified in HLA-DR4 (DRB1*0401) Transgenic Mice Are Encephalitogenic and Are Presented By Human B Cells. J Immunol. 2001 Dec 15;167(12):7119-25. PubMed PMID: 11739534.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - T cell epitopes of human myelin oligodendrocyte glycoprotein identified in HLA-DR4 (DRB1*0401) transgenic mice are encephalitogenic and are presented by human B cells. AU - Forsthuber,T G, AU - Shive,C L, AU - Wienhold,W, AU - de Graaf,K, AU - Spack,E G, AU - Sublett,R, AU - Melms,A, AU - Kort,J, AU - Racke,M K, AU - Weissert,R, PY - 2001/12/12/pubmed PY - 2002/1/5/medline PY - 2001/12/12/entrez SP - 7119 EP - 25 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 167 IS - 12 N2 - Myelin oligodendrocyte glycoprotein (MOG) is an Ag present in the myelin sheath of the CNS thought to be targeted by the autoimmune T cell response in multiple sclerosis (MS). In this study, we have for the first time characterized the T cell epitopes of human MOG restricted by HLA-DR4 (DRB1*0401), an MHC class II allele associated with MS in a subpopulation of patients. Using MHC binding algorithms, we have predicted MOG peptide binding to HLA-DR4 (DRB1*0401) and subsequently defined the in vivo T cell reactivity to overlapping MOG peptides by testing HLA-DR4 (DRB1*0401) transgenic mice immunized with recombinant human (rh)MOG. The data indicated that MOG peptide 97-108 (core 99-107, FFRDHSYQE) was the immunodominant HLA-DR4-restricted T cell epitope in vivo. This peptide has a high in vitro binding affinity for HLA-DR4 (DRB1*0401) and upon immunization induced severe experimental autoimmune encephalomyelitis in the HLA-DR4 transgenic mice. Interestingly, the same peptide was presented by human B cells expressing HLA-DR4 (DRB1*0401), suggesting a role for the identified MOG epitopes in the pathogenesis of human MS. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/11739534/T_cell_epitopes_of_human_myelin_oligodendrocyte_glycoprotein_identified_in_HLA_DR4__DRB1_0401__transgenic_mice_are_encephalitogenic_and_are_presented_by_human_B_cells_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=11739534 DB - PRIME DP - Unbound Medicine ER -