Myasthenia gravis patients, but not healthy subjects, recognize epitopes that are unique to the epsilon-subunit of the acetylcholine receptor.
Myasthenia gravis (MG) is an autoimmune disease characterized by deficits in neuromuscular transmission due to antibody-mediated damage of the acetylcholine receptor (AChR). We examined the in vitro immune response of peripheral blood mononuclear cells isolated from MG patients (n=38) and healthy nonmyasthenic subjects (n=31) to epitopes on the alpha-, epsilon-, and gamma-chains of the AChR. The epsilon- and gamma-epitopes tested represent regions with little sequence homology to the alpha-chain, and little sequence homology between the epsilon- and gamma-chains. No differences were observed in the immune response of MG patients and healthy subjects to any of the alpha-chain epitopes tested. Serial studies of the immune response to the alpha-peptides suggest that epitope spread does occur over time. Cells from MG patients were stimulated by the epsilon- and gamma-chain peptides, although the response was weaker than that to the alpha-peptides. Cells from healthy subjects showed reactivity to gamma-chain peptides only; none of the healthy subjects responded to the epsilon-chain peptides tested. Differences between the epsilon- and gamma-chains may be important in the development of MG, because only MG patients respond to epitopes that are unique to the epsilon-subunit.
Ragheb
Samia
S
Department of Neurology and Immunology, Wayne State University School of Medicine, 3128 Elliman Building, 421 East Canfield Ave., Detroit, Michigan 42801, USA. sragheb@med.wayne.edu
Mohamed
Mahmoud
M
Lisak
Robert P
RP
D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002417:Cattle; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000276:immunology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology; D021122:Protein Subunits / Q000138:chemical synthesis / Q000276:immunology / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000276:immunology / Q000502:physiology*
D016056:Immunodominant Epitopes; D008934:Mitogens; D010446:Peptide Fragments; D021122:Protein Subunits; D011978:Receptors, Nicotinic