T cell epitope spreading to myelin oligodendrocyte glycoprotein in HLA-DR4 transgenic mice during experimental autoimmune encephalomyelitis

Epitope spreading has been implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and human multiple sclerosis (MS). T cell epitope spreading has been demonstrated in rodents for myelin basic protein (MBP) and proteolipid protein (PLP) determinants, but not for myelin olig...

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Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 111(2004), 1 vom: 01. Apr., Seite 53-60
1. Verfasser: Klehmet, Juliane (VerfasserIn)
Weitere Verfasser: Shive, Carey, Guardia-Wolff, Rocio, Petersen, Ines, Spack, Edward G, Boehm, Bernhard O, Weissert, Robert, Forsthuber, Thomas G
Format: Aufsatz
Sprache:English
Veröffentlicht: 2004
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Epitopes, T-Lymphocyte HLA-DR4 Antigen MOG peptide 97-108 MOG protein, human Mog protein, mouse Myelin Proteins Myelin-Associated Glycoprotein mehr... Myelin-Oligodendrocyte Glycoprotein Peptide Fragments
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100 1 |a Klehmet, Juliane  |e verfasserin  |4 aut 
245 1 2 |a T cell epitope spreading to myelin oligodendrocyte glycoprotein in HLA-DR4 transgenic mice during experimental autoimmune encephalomyelitis 
264 1 |c 2004 
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520 |a Epitope spreading has been implicated in the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and human multiple sclerosis (MS). T cell epitope spreading has been demonstrated in rodents for myelin basic protein (MBP) and proteolipid protein (PLP) determinants, but not for myelin oligodendrocyte glycoprotein (MOG), another important myelin antigen. Moreover, the role of human autoimmunity-associated MHC molecules in epitope spreading, including HLA-DR2 and DR4, has not been formally examined. To address these questions, we investigated epitope spreading to MOG determinants in HLA-DR4 (DRB1*0401) transgenic mice during EAE. The data show that upon induction of EAE in HLA-DR4 transgenic mice with the immunodominant HLA-DR4-restricted MOG peptide 97-108 (MOG(97-108); TCFFRDHSYQEE), the T cell response diversifies over time to MOG(181-200) (core: MOG(183-191); FVIVPVLGP) and MBP. The spreading epitope MOG(181-200) binds with high affinity to HLA-DRB1*0401 and is presented by human HLA-DRB1*0401+antigen presenting cells. Moreover, this epitope is encephalitogenic in HLA-DRB1*0401 transgenic mice. This study demonstrates intra- and intermolecular epitope spreading to MOG and MBP in "humanized" HLA-DR4 transgenic mice 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Research Support, U.S. Gov't, P.H.S. 
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650 7 |a HLA-DR4 Antigen  |2 NLM 
650 7 |a MOG peptide 97-108  |2 NLM 
650 7 |a MOG protein, human  |2 NLM 
650 7 |a Mog protein, mouse  |2 NLM 
650 7 |a Myelin Proteins  |2 NLM 
650 7 |a Myelin-Associated Glycoprotein  |2 NLM 
650 7 |a Myelin-Oligodendrocyte Glycoprotein  |2 NLM 
650 7 |a Peptide Fragments  |2 NLM 
700 1 |a Shive, Carey  |e verfasserin  |4 aut 
700 1 |a Guardia-Wolff, Rocio  |e verfasserin  |4 aut 
700 1 |a Petersen, Ines  |e verfasserin  |4 aut 
700 1 |a Spack, Edward G  |e verfasserin  |4 aut 
700 1 |a Boehm, Bernhard O  |e verfasserin  |4 aut 
700 1 |a Weissert, Robert  |e verfasserin  |4 aut 
700 1 |a Forsthuber, Thomas G  |e verfasserin  |4 aut 
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