title: Four different synthetic peptides of proteolipid protein induce a distinct antibody response in MP4-induced experimental autoimmune encephalomyelitis.
abstract: Here we studied the autoantibody specificity elicited by proteolipid protein (PLP) in MP4-induced experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis (MS). In C57BL/6 (B6) mice, antibodies were induced by immunization with one of the two extracellular and by the intracellular PLP domain. Antibodies against extracellular PLP were myelin-reactive in oligodendrocyte cultures and induced mild spinal cord demyelination upon transfer into B cell-deficient J(H)T mice. Remarkably, also antibodies against intracellular PLP showed binding to intact oligodendrocytes and were capable of inducing myelin pathology upon transfer into J(H)T mice. In MP4-immunized mice peptide-specific T(H)1/T(H)17 responses were mainly directed against the extracellular PLP domains, but also involved the intracellular epitopes. These data suggest that both extracellular and intracellular epitopes of PLP contribute to the pathogenesis of MP4-induced EAE already in the setting of intact myelin. It remains to be elucidated if this concept also applies to MS itself.
authors.affiliation: Department of Anatomy II (Neuroanatomy), University of Cologne, Kerpener Straβe 62, 50924 Cologne, Germany.
authors.forename: Mascha S
authors.initials: MS
authors.lastname: Recks
authors.affiliation: Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr. 6, 97070 Wuerzburg, Germany.
authors.forename: Nicolai B
authors.initials: NB
authors.lastname: Grether
authors.affiliation: Department of Anatomy I, University of Cologne, Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: van der Broeck
authors.affiliation: Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr. 6, 97070 Wuerzburg, Germany.
authors.forename: Alla
authors.initials: A
authors.lastname: Ganscher
authors.affiliation: Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr. 6, 97070 Wuerzburg, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Wagner
authors.affiliation: Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr. 6, 97070 Wuerzburg, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Henke
authors.affiliation: Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr. 6, 97070 Wuerzburg, Germany.
authors.forename: Süleyman
authors.initials: S
authors.lastname: Ergün
authors.affiliation: Department of Neurology, University of Cologne, Kerpener Str. 62, 50924 Cologne, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Schroeter
authors.affiliation: Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr. 6, 97070 Wuerzburg, Germany. Electronic address: stefanie.kuerten@uni-wuerzburg.de.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kuerten
mesh_terms: D000818:Animals; D003711:Demyelinating Diseases / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology*; D018991:Myelin Proteolipid Protein / Q000276:immunology*; D009836:Oligodendroglia / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000939:Epitopes; C101821:MP4 protein, chimeric; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins
keywords: Animal models; Antibodies; Autoimmunity; B cells; Multiple sclerosis