Myelin oligodendrocyte glycoprotein-35-55 peptide induces severe chronic experimental autoimmune encephalomyelitis in HLA-DR2-transgenic mice.
The use of HLA class II-transgenic (Tg) mice has facilitated identification of antigenic T cell epitopes that may contribute to inflammation in T cell-mediated diseases such as rheumatoid arthritis and multiple sclerosis (MS). In this study, we compared the encephalitogenic activity of three DR2-res...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2004
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| _version_ | 1826300443224965120 |
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| author | Rich, C Link, J Zamora, A Jacobsen, H Meza-Romero, R Offner, H Jones, R Burrows, G Fugger, L Vandenbark, A |
| author_facet | Rich, C Link, J Zamora, A Jacobsen, H Meza-Romero, R Offner, H Jones, R Burrows, G Fugger, L Vandenbark, A |
| author_sort | Rich, C |
| collection | OXFORD |
| description | The use of HLA class II-transgenic (Tg) mice has facilitated identification of antigenic T cell epitopes that may contribute to inflammation in T cell-mediated diseases such as rheumatoid arthritis and multiple sclerosis (MS). In this study, we compared the encephalitogenic activity of three DR2-restricted myelin determinants [mouse (m) myelin oligodendrocyte glycoprotein (MOG)-35-55, human (h)MOG-35-55 and myelin basic protein (MBP)-87-99] in Tg mice expressing the MS-associated DR2 allele, DRB1*1501. We found that mMOG-35-55 peptide was strongly immunogenic and induced moderately severe chronic experimental autoimmune encephalomyelitis (EAE) with white matter lesions after a single injection in Freund's complete adjuvant followed by pertussis toxin. hMOG-35-55 peptide,which differs from mMOG-35-55 peptide by a proline for serine substitution at position 42, was also immunogenic, but not encephalitogenic, and was only partially cross-reactive with mMOG-35-55. In contrast, MBP-87-99, which can induce EAE in double-Tg mice expressing both HLA-DR2 and a human MBP-specific TCR, was completely non-encephalitogenic in HLA-DR2-Tg mice lacking the human TCR transgene. These findings demonstrate potent encephalitogenic activity of the mMOG-35-55 peptide in association with HLA-DR2, thus providing a strong rationale for further study of hMOG-35-55 peptide as a potential pathogenic determinant in humans. |
| first_indexed | 2024-03-07T05:17:15Z |
| format | Journal article |
| id | oxford-uuid:dda3eb8d-b751-4204-8d73-ee28f858913f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:17:15Z |
| publishDate | 2004 |
| record_format | dspace |
| spelling | oxford-uuid:dda3eb8d-b751-4204-8d73-ee28f858913f2022-03-27T09:26:27ZMyelin oligodendrocyte glycoprotein-35-55 peptide induces severe chronic experimental autoimmune encephalomyelitis in HLA-DR2-transgenic mice.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dda3eb8d-b751-4204-8d73-ee28f858913fEnglishSymplectic Elements at Oxford2004Rich, CLink, JZamora, AJacobsen, HMeza-Romero, ROffner, HJones, RBurrows, GFugger, LVandenbark, AThe use of HLA class II-transgenic (Tg) mice has facilitated identification of antigenic T cell epitopes that may contribute to inflammation in T cell-mediated diseases such as rheumatoid arthritis and multiple sclerosis (MS). In this study, we compared the encephalitogenic activity of three DR2-restricted myelin determinants [mouse (m) myelin oligodendrocyte glycoprotein (MOG)-35-55, human (h)MOG-35-55 and myelin basic protein (MBP)-87-99] in Tg mice expressing the MS-associated DR2 allele, DRB1*1501. We found that mMOG-35-55 peptide was strongly immunogenic and induced moderately severe chronic experimental autoimmune encephalomyelitis (EAE) with white matter lesions after a single injection in Freund's complete adjuvant followed by pertussis toxin. hMOG-35-55 peptide,which differs from mMOG-35-55 peptide by a proline for serine substitution at position 42, was also immunogenic, but not encephalitogenic, and was only partially cross-reactive with mMOG-35-55. In contrast, MBP-87-99, which can induce EAE in double-Tg mice expressing both HLA-DR2 and a human MBP-specific TCR, was completely non-encephalitogenic in HLA-DR2-Tg mice lacking the human TCR transgene. These findings demonstrate potent encephalitogenic activity of the mMOG-35-55 peptide in association with HLA-DR2, thus providing a strong rationale for further study of hMOG-35-55 peptide as a potential pathogenic determinant in humans. |
| spellingShingle | Rich, C Link, J Zamora, A Jacobsen, H Meza-Romero, R Offner, H Jones, R Burrows, G Fugger, L Vandenbark, A Myelin oligodendrocyte glycoprotein-35-55 peptide induces severe chronic experimental autoimmune encephalomyelitis in HLA-DR2-transgenic mice. |
| title | Myelin oligodendrocyte glycoprotein-35-55 peptide induces severe chronic experimental autoimmune encephalomyelitis in HLA-DR2-transgenic mice. |
| title_full | Myelin oligodendrocyte glycoprotein-35-55 peptide induces severe chronic experimental autoimmune encephalomyelitis in HLA-DR2-transgenic mice. |
| title_fullStr | Myelin oligodendrocyte glycoprotein-35-55 peptide induces severe chronic experimental autoimmune encephalomyelitis in HLA-DR2-transgenic mice. |
| title_full_unstemmed | Myelin oligodendrocyte glycoprotein-35-55 peptide induces severe chronic experimental autoimmune encephalomyelitis in HLA-DR2-transgenic mice. |
| title_short | Myelin oligodendrocyte glycoprotein-35-55 peptide induces severe chronic experimental autoimmune encephalomyelitis in HLA-DR2-transgenic mice. |
| title_sort | myelin oligodendrocyte glycoprotein 35 55 peptide induces severe chronic experimental autoimmune encephalomyelitis in hla dr2 transgenic mice |
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