title: Suppression of MOG- and PLP-induced experimental autoimmune encephalomyelitis using a novel multivalent bifunctional peptide inhibitor.
abstract: Previously, bifunctional peptide inhibitors (BPI) with a single antigenic peptide have been shown to suppress experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner. In this study, a multivalent BPI (MVBMOG/PLP) with two antigenic peptides derived from myelin oligodendrocyte glycoprotein (MOG38-50) and myelin proteolipid protein (PLP139-151) was evaluated in suppressing MOG38-50- and PLP139-151-induced EAE. MVBMOG/PLP significantly suppressed both models of EAE even when there was some evidence of epitope spreading in the MOG38-50-induced EAE model. In addition, MVBMOG/PLP was found to be more effective than PLP-BPI and MOG-BPI in suppressing MOG38-50-induced EAE. Thus, the development of MVB molecules with broader antigenic targets can lead to suppression of epitope spreading in EAE.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KS 66047, United States.
authors.forename: Ahmed H
authors.initials: AH
authors.lastname: Badawi
authors.forename: Teruna J
authors.initials: TJ
authors.lastname: Siahaan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D000939:Epitopes / Q000502:physiology; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D018991:Myelin Proteolipid Protein / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D010455:Peptides
chemical_list: D000939:Epitopes; C571327:Mog protein, mouse; D018991:Myelin Proteolipid Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; C573814:PLP-BPI peptide; D010446:Peptide Fragments; D010455:Peptides; C047516:Plp1 protein, mouse; C435023:myelin proteolipid protein (139-151)
keywords: Antigen-presenting cell; BPI; Bifunctional peptide inhibitor; EAE; Epitope spreading; Experimental autoimmune encephalomyelitis; MOG; MVB; PLP; T cell; bifunctional peptide inhibitor; experimental autoimmune encephalomyelitis; multivalent BPI; myelin oligodendrocyte glycoprotein; proteolipid protein
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