T Cell Epitopes of Human Myelin Oligodendrocyte Glycoprotein Identified in HLA-DR4 (DRB10401) Transgenic Mice Are Encephalitogenic and Are Presented by Human B Cells

• Published in: The Journal of immunology (1950) Vol. 167; no. 12; pp. 7119 - 7125
• Main Authors: Forsthuber, Thomas G, Shive, Carey L, Wienhold, Wolfgang, de Graaf, Katrien, Spack, Edward G, Sublett, Robert, Melms, Arthur, Kort, Jens, Racke, Michael K, Weissert, Robert
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.12.2001
• Subjects: Amino Acid Sequence; Animals; Antigen Presentation; Autoantigens - chemistry; Autoantigens - immunology; Autoantigens - metabolism; B-Lymphocytes - immunology; Binding, Competitive; CD4-Positive T-Lymphocytes - immunology; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - pathology; Epitope Mapping; Epitopes, T-Lymphocyte - immunology; Epitopes, T-Lymphocyte - metabolism; HLA-DR Antigens - genetics; HLA-DR Antigens - metabolism; HLA-DRB1 Chains; Humans; Immunodominant Epitopes; Kinetics; Mice; Mice, Transgenic; Multiple Sclerosis - immunology; Myelin oligodendrocyte glycoprotein; Myelin Proteins; Myelin-Associated Glycoprotein - chemistry; Myelin-Associated Glycoprotein - immunology; Myelin-Associated Glycoprotein - metabolism; Myelin-Associated Glycoprotein - pharmacology; Peptide Fragments - immunology; Peptide Fragments - metabolism; Peptide Fragments - pharmacology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.12.7119

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.