Myelin oligodendrocyte glycoprotein-35-55 peptide induces severe chronic experimental autoimmune encephalomyelitis in HLA-DR2-transgenic mice

Cathleen Rich, Jason M. Link, Alex Zamora, Helle Jacobsen, Roberto Meza-Romero, Halina Offner, Richard Jones, Gregory G. Burrows, Lars Fugger, Arthur A. Vandenbark

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

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, DRB11501. 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.

Original languageEnglish (US)
Pages (from-to)1251-1261
Number of pages11
JournalEuropean Journal of Immunology
Volume34
Issue number5
DOIs
StatePublished - May 2004

Keywords

  • CNS inflammation
  • Experimental autoimmune encephalomyelitis
  • HLA-DR2-transgenic mice
  • MOG peptide
  • T cell activation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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