Immunity to the extracellular domain of nogo-a modulates experimental autoimmune encephalomyelitis

Paulo Fontoura, Peggy P. Ho, Jason Devoss, Binhai Zheng, Byung J. Lee, Brian A. Kidd, Hideki Garren, Raymond A. Sobel, William H. Robinson, Marc Tessier-Lavigne, Lawrence Steinman

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


Nogo-66, the extracellular 66 aa loop of the Nogo-A protein found in CNS myelin, interacts with the Nogo receptor and has been proposed to mediate inhibition of axonal regrowth. It has been shown that immunization with Nogo-A promotes recovery in animal models of spinal cord injury through induction of Ab production. In this report, studies were performed to characterize the immune response to Nogo-66 and to determine the role of Nogo in experimental autoimmune encephalomyelitis (EAE). Immunization of EAE-susceptible mouse strains with peptides derived from Nogo-66 induced a CNS immune response with clinical and pathological similarities to EAE. The Nogo-66 peptides elicited strong T cell responses that were not cross-reactive to other encephalitogenic myelin Ags. Using a large scale spotted microarray containing proteins and peptides derived from a wide spectrum of myelin components, we demonstrated that Nogo-66 peptides also generated a specific Ab response that spreads to several other encephalitogenic myelin Ags following immunization. Nogo-66-specific T cell lines ameliorated established EAE, via Nogo-66-specific Th2 cells that entered the CNS. These results indicate that some T cell and B cell immune responses to Nogo-66 are associated with suppression of ongoing EAE, whereas other Nogo-66 epitopes can be encephalitogenic.

Original languageEnglish
Pages (from-to)6981-6992
Number of pages12
JournalJournal of Immunology
Issue number11
StatePublished - 1 Dec 2004
Externally publishedYes


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