Characterization of a protein with an acetylcholine receptor epitope from myasthenia gravis-associated thymomas.
Immunohistochemical studies have shown that almost all thymomas of myasthenia gravis patients contain at least one protein sharing an antigenic determinant with the nicotinic acetylcholine receptor (AchR) of human muscle. We describe the characterization of this protein (p153) which has a molecular weight of 153 and an isoelectric point of 5.0. By treatment of p153 with endoglycosidases, no significant glycosylation has been detected. Immunologically, p153 crossreacts with monoclonal antibodies against the amino acid sequence 371-378 of the alpha-chain of the AchR. No cross-reactivity to the main immunogenic region of the AchR nor an alpha-bungarotoxin binding site are found. By Western blotting, p153 was generally neither detectable in normal tissues nor extrathymic tumors with the exception of paraganglioma and neuroblastoma. In conclusion, the structure of p153 is apparently unrelated to the AchR from muscle or the alpha-bungarotoxin binding proteins from thymoma. Since there is no evidence for an AchR expression in thymoma, the antigenic homology of p153 with the nicotinic AchR might be relevant for triggering an intrathymomatous autosensitization of maturing T cells and could be responsible for the high association of thymomas with myasthenia gravis.
Institute of Pathology, University of Würzburg, Federal Republic of Germany.
A
A
Marx
R
R
O'Connor
K I
KI
Geuder
F
F
Hoppe
B
B
Schalke
S
S
Tzartos
I
I
Kalies
T
T
Kirchner
H K
HK
Müller-Hermelink
D000911:Antibodies, Monoclonal; D002038:Bungarotoxins / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D000939:Epitopes; D006801:Humans; D009157:Myasthenia Gravis / Q000150:complications*; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000276:immunology*; D013945:Thymoma / Q000209:etiology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D002038:Bungarotoxins; D000939:Epitopes; D009363:Neoplasm Proteins; D011950:Receptors, Cholinergic