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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antigen Presentation*
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Autoantigens / chemistry
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Autoantigens / immunology
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Autoantigens / metabolism
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B-Lymphocytes / immunology*
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Binding, Competitive
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CD4-Positive T-Lymphocytes / immunology
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Epitope Mapping
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Epitopes, T-Lymphocyte / immunology*
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Epitopes, T-Lymphocyte / metabolism
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HLA-DR Antigens / genetics*
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HLA-DR Antigens / metabolism
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HLA-DRB1 Chains
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Humans
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Immunodominant Epitopes
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Kinetics
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Mice
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Mice, Transgenic
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Multiple Sclerosis / immunology*
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Myelin Proteins
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Myelin-Associated Glycoprotein / chemistry
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Myelin-Associated Glycoprotein / immunology*
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Myelin-Associated Glycoprotein / metabolism
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Myelin-Associated Glycoprotein / pharmacology
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
Substances
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Autoantigens
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Epitopes, T-Lymphocyte
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HLA-DR Antigens
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HLA-DRB1 Chains
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HLA-DRB1*04:01 antigen
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Immunodominant Epitopes
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MOG peptide 97-108
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MOG protein, human
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Mog protein, mouse
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Myelin Proteins
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Myelin-Associated Glycoprotein
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments