MHC class II presentation of human acetylcholine receptor in Myasthenia gravis: binding of synthetic gamma subunit sequences to DR molecules.
Embryonic muscle acetylcholine receptor (AChR) is composed of four subunits-alpha, beta, gamma, and delta. Upon innervation, the gamma subunit is substituted by a homologous epsilon subunit. Embryonic muscle AChR might be the original autoantigen in Myasthenia gravis (MG) because it is expressed in the thymus, where the anti-AChR response might start, as well as in adult extrinsic ocular muscles, which are a preferential target in MG. MG patients have antibodies specific for embryonic AChR and CD4+ T cells, which recognize epitopes on the gamma subunit, in association with DR molecules. In the present study, we investigated the binding to several purified DR molecules (DRB1*0101, DRB1*0201, DRB1*0401 and DRB1*0701) of overlapping synthetic peptides, screening the human gamma subunit sequence. Binding of the peptides to the DR molecules were determined from their ability to compete with radiolabelled peptide probes for binding to purified DR molecules. All peptides which were recognized by CD4+ cells bound to the relevant DR molecule. On the other hand, some AChR peptides not recognized by CD4+ cells of MG patients bound well to one or more DR molecules. In terms of relative ability to bind to the DR molecules tested, the gamma subunit behaved like an exogenous antigen: some AChR peptide sequences uniquely bound one DR molecule, others bound several DR alleles, while others did not bind any of the DR molecules tested.
Yuen
M H
MH
Department of Biochemistry, College of Biological Sciences, University of Minnesota, St. Paul 55108, USA.
Macklin
K D
KD
Conti-Fine
B M
BM
D000109:Acetylcholine / Q000276:immunology; D000595:Amino Acid Sequence; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002846:Chromatography, Affinity; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D009157:Myasthenia Gravis / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D011950:Receptors, Cholinergic / Q000737:chemistry* / Q000276:immunology
D006684:HLA-DR Antigens; D011950:Receptors, Cholinergic; D000109:Acetylcholine