Localization of the Main Immunogenic Region of Human Muscle Acetylcholine Receptor to Residues 67-76 of the α Subunit

• Published in: Proceedings of the National Academy of Sciences - PNAS 1988-05, Vol.85 (9), p.2899-2903
• Main Authors: Tzartos, Socrates J., Kokla, Anna, Walgrave, Susan L., Conti-Tronconi, Bianca M.
• Format: Article
• Language: English
• Subjects: acetylcholine; Amino Acid Sequence; Amino acids; Antibodies; Antibodies, Monoclonal; Antigens; Binding sites; Binding, Competitive; Biochemistry; Biological and medical sciences; Cell physiology; Cholinergic receptors; Chromatography, High Pressure Liquid; Epitopes; Fundamental and applied biological sciences. Psychology; Humans; man; Molecular and cellular biology; Molecular Sequence Data; monoclonal antibodies; Muscles - analysis; neuromuscular junctions; Neurotransmission; Peptide Fragments - immunology; Peptide Mapping; Phosphates; Radioactive decay; Radioimmunoassay; Reactivity; Receptors, Cholinergic - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.85.9.2899

The majority of antibodies to the acetylcholine receptor (AcChoR), both in the human disease myasthenia gravis and in its experimental models, are directed against an extracellular area of the AcChoR α subunit called the main immunogenic region (MIR). We have studied the binding of anti-AcChoR monoclonal antibodies (mAbs) to 26 synthetic peptides corresponding to the hydrophilic parts of the human AcChoR α subunit. The binding sites for eight anti-MIR mAbs and for eight anti-α -subunit, non-anti-MIR mAbs were localized. Anti-MIR mAbs bound to one peptide corresponding to residues 63-80 of the human α subunit. A second panel of peptides corresponding to the various parts of the α -subunit segment 63-80 was synthesized. Anti-MIR antibodies bound to a peptide that contained the α -subunit sequence 67-76. Thus, a main constituent loop of the MIR is localized between residues 67 and 76 of the α subunit.