Immunity to the extracellular domain of Nogo-A modulates experimental autoimmune encephalomyelitis.
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.
Fontoura
Paulo
P
Department of Neurology and Neurological Sciences, School of Medicine, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. pfontoura@igc-gulbenkian.pt
Ho
Peggy P
PP
DeVoss
Jason
J
Zheng
Binhai
B
Lee
Byung J
BJ
Kidd
Brian A
BA
Garren
Hideki
H
Sobel
Raymond A
RA
Robinson
William H
WH
Tessier-Lavigne
Marc
M
Steinman
Lawrence
L
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D004198:Disease Susceptibility; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005110:Extracellular Space / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D000070798:Nogo Proteins; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D020033:Protein Isoforms / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation
D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D009185:Myelin Proteins; D000070798:Nogo Proteins; D010446:Peptide Fragments; D020033:Protein Isoforms; C000603201:Rtn4 protein, mouse