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Mouse MOG35-55 (MOG) is a myelin-specific neuroantigen that mimics MS when immunized into SJL or C57BL/6 mice. MOG-immunized mice develop a severe EAE with approximately 100% incidence, mortality, and morbidity. The neuroantigen presents MHC class II-restricted epitopes, including a highly conserved peptide (35-55) that has been proposed to mediate the pathogenic effector functions. Therefore, it was of interest to determine whether MOG peptide 35-55 could serve as a substitute for myelin oligodendrocyte glycoprotein (MOG) to induce EAE in SJL mice and in MOG KO mice. We examined whether adoptively transferred MOG-primed MOG KO splenocytes can induce EAE. MOG35-55 induced EAE in 100% of MOG KO mice, whereas SJL and MOG35-55-primed MOG KO splenocytes never induced EAE. CD27 signaling is known to mediate T-cell responses and is functionally associated with autoimmune diseases. We find that both MOG peptide 35-55 and MOG protein 35-55 are biologically active in inducing EAE in mice, and that this activity was dependent on the presence of both MHC class II and CD4(+) T cells. Transgenic mice expressing CD30 were used to test the requirement of CD30 expression in T cells in the development of MOG35-55-induced EAE. CD30 transgenic mice developed EAE with a low incidence and were capable of transferring the disease to MOG35-55-immunized mice. The MHC class II-restricted MOG35-55 epitope influences T-cell costimulation through its interaction with CD4. Our data suggest that the CD27 signaling pathway may play a central role in the development of EAE.1. Field of the Invention
The present invention relates to a process for preparing unsymmetrical bis(beta-mercapto-m-tolyl) and fumarate derivatives of 4-cy
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