Abstract | OBJECTIVE: METHODS: T-cell recognition in mice was examined using overlapping peptides and intact full-length mouse MOG. EAE was evaluated by peptide immunization and by adoptive transfer of MOG epitope-specific T cells. Frequency of epitope-specific T cells was examined by ELISPOT. RESULTS: Three T-cell determinants of MOG were discovered in its transmembrane and cytoplasmic domains, p119-132, p181-195, and p186-200. Transmembrane MOG p119-132 induced clinical EAE, CNS inflammation, and demyelination as potently as p35-55 in C57BL/6 mice and other H-2(b) strains. p119-128 contained its minimal encephalitogenic epitope. p119-132 did not cause disease in EAE-susceptible non-H-2(b) strains, including Biozzi, NOD, and PL/J. MOG p119-132-specific T cells produced Th1 and Th17 cytokines and transferred EAE to wild-type recipient mice. After immunization with full-length MOG, a significantly higher frequency of MOG-reactive T cells responded to p119-132 than to p35-55, demonstrating that p119-132 is an immunodominant encephalitogenic epitope. MOG p181-195 did not cause EAE, and MOG p181-195-specific T cells could not transfer EAE into wild-type or highly susceptible T- and B-cell-deficient mice. CONCLUSIONS: Transmembrane and cytoplasmic domains of MOG contain immunodominant T-cell epitopes in EAE. A CNS autoantigen can also contain nonpathogenic stimulatory T-cell epitopes. Recognition that a myelin antigen contains multiple encephalitogenic and nonencephalitogenic determinants may have implications for therapeutic development in MS.
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Authors | Aparna Shetty, Sheena G Gupta, Michel Varrin-Doyer, Martin S Weber, Thomas Prod'homme, Nicolas Molnarfi, Niannian Ji, Patricia A Nelson, Juan C Patarroyo, Ulf Schulze-Topphoff, Stephen E Fogal, Thomas Forsthuber, Raymond A Sobel, Claude C A Bernard, Anthony J Slavin, Scott S Zamvil |
Journal | Neurology(R) neuroimmunology & neuroinflammation
(Neurol Neuroimmunol Neuroinflamm)
Vol. 1
Issue 2
Pg. e22
(Aug 2014)
ISSN: 2332-7812 [Print] United States |
PMID | 25340074
(Publication Type: Journal Article)
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