Myasthenogenicity in the main immunogenic region of acetylcholine receptor as modified by conformational design: an approach to antigenic synthetic peptides

• Published in: Journal of the neurological sciences Vol. 109; no. 2; pp. 182 - 187
• Main Authors: Takamori, Masaharu, Hamada, Toshio, Okumura, Sei'ichi
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 01.06.1992; Elsevier Science
• Subjects: Acetylcholine receptor; Amino Acid Sequence; Animals; Antibody; Biological and medical sciences; Diseases of striated muscles. Neuromuscular diseases; Electrophysiology; Female; Immunogen; Medical sciences; Molecular Sequence Data; Molecular structure; Motor Endplate - drug effects; Muscle Denervation; Myasthenia gravis; Myasthenia Gravis - immunology; Neurology; Peptides - immunology; Protein Conformation; Rats; Receptors, Cholinergic - immunology; Synthetic peptides; Torpedo; Synthetic peptides; Myasthenia gravis; Molecular structure; Antibody; Acetylcholine receptor; Immunogen; Immunopathology; Striated muscle disease; Nervous system diseases; Cholinergic receptor; Immunogenicity; Immunological investigation; Animal; Autoimmune disease
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/0022-510X(92)90166-I

Myasthenogenic regions in the acetylcholine receptor (AChR) α-subunit were studied in view of the conformation-dependent B-cell epitope expected at β-turn and the MHC class II-restricted T-cell epitope expected at α-helix. Torpedo AChR α67–76 and α107–116 were synthetized as the main immunogenic region and the site specific for T-cell epitope in Lewis rat, respectively. Model peptides, synthetized 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 terns of antigenic conformation. The model peptide, α107–116·α67–76·α107–116, 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, α107–116·α67–76 and/or α107–116·NPGG·α67–76 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.