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Structural characterization of the main immunogenic region of the Torpedo acetylcholine receptor.
- Source :
-
Molecular immunology [Mol Immunol] 2014 Mar; Vol. 58 (1), pp. 116-31. Date of Electronic Publication: 2013 Dec 11. - Publication Year :
- 2014
-
Abstract
- To develop antigen-specific immunotherapies for autoimmune diseases, knowledge of the molecular structure of targeted immunological hotspots will guide the production of reagents to inhibit and halt production of antigen specific attack agents. To this end we have identified three noncontiguous segments of the Torpedo nicotinic acetylcholine receptor (AChR) α-subunit that contribute to the conformationally sensitive immunological hotspot on the AChR termed the main immunogenic region (MIR): α(1-12), α(65-79), and α(110-115). This region is the target of greater than 50% of the anti-AChR Abs in serum from patients with myasthenia gravis (MG) and animals with experimental autoimmune myasthenia gravis (EAMG). Many monoclonal antibodies (mAbs) raised in one species against an electric organ AChR cross react with the neuromuscular AChR MIR in several species. Probing the Torpedo AChR α-subunit with mAb 132A, a disease inducing anti-MIR mAb raised against the Torpedo AChR, we have determined that two of the three MIR segments, α(1-12) and α(65-79), form a complex providing the signature components recognized by mAb 132A. These two segments straddle a third, α(110-115), that seems not to contribute specific side chains for 132A recognition, but is necessary for optimum antibody binding. This third segment appears to form a foundation upon which the three-dimensional 132A epitope is anchored.<br /> (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Animals
Antibodies, Monoclonal immunology
Binding Sites, Antibody immunology
Green Fluorescent Proteins genetics
Humans
Molecular Sequence Data
Myasthenia Gravis blood
Peptide Fragments immunology
Protein Binding immunology
Protein Conformation
Protein Structure, Tertiary
Receptors, Nicotinic immunology
Recombinant Fusion Proteins genetics
Sequence Analysis, Protein
Torpedo
Myasthenia Gravis immunology
Receptors, Nicotinic chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9142
- Volume :
- 58
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 24333757
- Full Text :
- https://doi.org/10.1016/j.molimm.2013.11.005