title: Autoantigen conformation influences both B- and T-cell responses and encephalitogenicity.
abstract: It has become increasingly clear that only antibodies recognizing conformation-dependent epitopes of myelin oligodendrocyte glycoprotein (MOG) have a demyelinating potential in the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Nevertheless, for the induction of EAE, most studies to date have used MOG peptides or bacterially expressed MOG, neither of which contain the tertiary structure of the native antigen. Non-refolded recombinant human MOG does not induce EAE in DA rats. Therefore, we refolded this protein in order to assess the influence of MOG conformation on its pathogenicity in DA rats. DA rats immunized with refolded human MOG developed severe acute EAE. As expected, rats immunized with the refolded protein had a higher amount of conformational MOG antibodies present in serum. But in addition, a striking effect of MOG refolding on the generation of T-cell responses was found. Indeed, T-cell responses against the encephalitogenic MOG 91-108 epitope were greatly enhanced after refolding. Therefore, we conclude that refolding of MOG increases its pathogenicity both by generating conformation-dependent MOG antibodies and by enhancing its processing or/and presentation on MHC molecules. These data are important in regard to investigations of the pathogenic potential of many (auto)antigens.
authors.affiliation: Experimental Neuroimmunology Laboratory, Hertie Institute for Clinical Brain Research, Eberhard Karls University Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Katrien L
authors.initials: KL
authors.lastname: de Graaf
authors.affiliation: Experimental Neuroimmunology Laboratory, Hertie Institute for Clinical Brain Research, Eberhard Karls University Tuebingen, D-72076 Tuebingen, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Albert
authors.affiliation: Experimental Neuroimmunology Laboratory, Hertie Institute for Clinical Brain Research, Eberhard Karls University Tuebingen, D-72076 Tuebingen, Germany. Electronic address: robert.weissert@klinik.uni-regensburg.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Weissert
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology* / Q000494:pharmacology; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D009185:Myelin Proteins / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D063308:Myelin-Oligodendrocyte Glycoprotein; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C571326:MOG protein, human; C571328:Mog protein, rat; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein