title: Amelioration of established experimental autoimmune encephalomyelitis by an MHC anchor-substituted variant of proteolipid protein 139-151.
abstract: Murine experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated autoimmune disorder directed against myelin proteins within the CNS. We propose that variant peptides containing amino acid substitutions at MHC anchor residues will provide a unique means to controlling the polyclonal autoimmune T cell response. In this study, we have identified an MHC variant of proteolipid protein (PLP) 139-151 (145D) that renders PLP(139-151)-specific T cell lines anergic in vitro, as defined by a significant reduction in proliferation and IL-2 production following challenge with wild-type peptide. In vivo administration of 145D before challenge with PLP(139-151) results in a significant reduction in disease severity and incidence. Importantly, we demonstrate the ability of an MHC variant peptide to ameliorate established EAE. An advantage to this treatment is that the MHC variant peptide does not induce an acute hypersensitivity reaction. This is in contrast to previous work in the PLP(139-151) model demonstrating that anaphylactic shock resulting in death occurs upon rechallenge with the encephalitogenic peptide. Taken together, these data demonstrate the effectiveness of MHC anchor-substituted peptides in the treatment of EAE and suggest their utility in the treatment of other autoimmune disorders.
authors.affiliation: Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
authors.forename: Carrie D
authors.initials: CD
authors.lastname: Margot
authors.forename: Mandy L
authors.initials: ML
authors.lastname: Ford
authors.forename: Brian D
authors.initials: BD
authors.lastname: Evavold
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D017635:Clonal Anergy; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D005260:Female; D014644:Genetic Variation; D007114:Immunization; D007167:Immunotherapy; D066298:In Vitro Techniques; D008285:Major Histocompatibility Complex; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; C435023:myelin proteolipid protein (139-151)