title: Lack of pathogenicity of immunodominant T and B cell determinants of the nicotinic acetylcholine receptor epsilon-chain.
abstract: The nicotinic acetylcholine receptor (nAChR) is the autoantigen in seropositive myasthenia gravis (MG) that is a T cell-dependent B cell-mediated autoimmune disorder. We tested the immunogenicity and myasthenogenicity of the extracellular and first transmembrane domain of the epsilon-chain(1-221) of the nAChR in inbred and MHC congenic rat strains. Immunodominant T and B cell determinants did not induce experimental autoimmune myasthenia gravis (EAMG), although immunization resulted in strong Th1 and B cell responses, which could be mapped with overlapping peptides of the nAChR epsilon-subunit in eight different rat strains. Our data underscores the concept that immunodominant autoantigen-specific T and B cell responses can lack pathogenicity in autoimmune disease and might be of relevance for the physiological integrity of the organism.
authors.affiliation: Experimental Neuroimmunology Laboratory, Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Gaertner
authors.forename: Katrien L
authors.initials: KL
authors.lastname: de Graaf
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wienhold
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Wiesmüller
authors.forename: Arthur
authors.initials: A
authors.lastname: Melms
authors.forename: Robert
authors.initials: R
authors.lastname: Weissert
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020296:Animals, Congenic; D001324:Autoantigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology; D010455:Peptides / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D011978:Receptors, Nicotinic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D001324:Autoantigens; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D011978:Receptors, Nicotinic