Immunodominant regions for T helper-cell sensitization on the human nicotinic receptor alpha subunit in myasthenia gravis.
In myasthenia gravis an autoimmune response against the nicotinic acetylcholine receptor (AChR) occurs. The alpha subunit of the AChR contains both the epitope(s) that dominates the antibody response (main immunogenic region) and epitopes involved in T helper cell sensitization. In this study, overlapping synthetic peptides corresponding to the complete AChR alpha-subunit sequence were used to propagate polyclonal AChR-specific T helper cell lines from four myasthenic patients of different HLA types. Response of the T helper lines to the individual peptides was studied. Four immunodominant sequence segments were identified--i.e., residues 48-67, 101-120, 304-322, and 419-437. These regions did not include residues known to form the main immunogenic region or the cholinergic binding site, and they frequently contained sequence motifs that have been proposed to be related to T-epitope formation.
Protti
M P
MP
Department of Biochemistry, College of Biological Sciences, University of Minnesota, Saint Paul 55108.
Manfredi
A A
AA
Straub
C
C
Howard
J F
JF
Conti-Tronconi
B M
BM
D000595:Amino Acid Sequence; D000818:Animals; D015704:CD4 Antigens / Q000032:analysis; D002460:Cell Line; D006684:HLA-DR Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics*; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000138:chemical synthesis; D011978:Receptors, Nicotinic / Q000235:genetics* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014101:Torpedo
D015704:CD4 Antigens; D006684:HLA-DR Antigens; D016056:Immunodominant Epitopes; D046911:Macromolecular Substances; D010455:Peptides; D011978:Receptors, Nicotinic