Myasthenogenicity in the main immunogenic region of acetylcholine receptor as modified by conformational design: an approach to antigenic synthetic peptides.
Myasthenogenic regions in the acetylcholine receptor (AChR) alpha-subunit were studied in view of the conformation-dependent B-cell epitope expected at beta-turn and the MHC class II-restricted T-cell epitope expected at alpha-helix. Torpedo AChR alpha 67-76 and alpha 107-116 were synthesized as the main immunogenic region and the site specific for T-cell epitope in Lewis rat, respectively. Model peptides, synthesized by combining these natural sequence segments or by intervening the segment aligned as Asn-Pro-Gly-Gly (NPGG) in natural sequence segments, were tested in terms of antigenic conformation. The model peptide, alpha 107-116.alpha 67-76.alpha 107-116, was immunogenic in the induction of the animal model of myasthenia, accompanied by the anti-peptide antibody cross-reactive with the native AChR. High antigenicity in antibody assays for various peptide- and native AChR-immunized rats was found when the model peptides, alpha 107-116.alpha 67-76 and/or alpha 107-116.NPGG.alpha 67-76 were used for measurement as antigens. Antigenic conformation for the induction of the disease may thus be different from that for the reactivity to antibody.
Takamori
M
M
Department of Neurology, Kanazawa University School of Medicine, Japan.
Hamada
T
T
Okumura
S
S
D000595:Amino Acid Sequence; D000818:Animals; D004594:Electrophysiology; D005260:Female; D008969:Molecular Sequence Data; D009045:Motor Endplate / Q000187:drug effects; D009121:Muscle Denervation; D009157:Myasthenia Gravis / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D011487:Protein Conformation; D051381:Rats; D011950:Receptors, Cholinergic / Q000276:immunology*; D014101:Torpedo
D010455:Peptides; D011950:Receptors, Cholinergic