Search for cross-reactive idiotypes on monoclonal and myasthenia gravis acetylcholine receptor antibodies.
Myasthenia gravis patients have serum anti-acetylcholine receptor antibodies that compete with monoclonal antibodies for binding to epitopes on the human acetylcholine receptor. To investigate the presence of shared idiotypes we immunised syngeneic mice with each of ten well-characterised monoclonal antibodies, previously raised against purified human acetylcholine receptor, and tested the polyclonal antisera and seven monoclonal anti-idiotype antibodies, for binding to the antigen-combining site, to framework idiotopes, and by ELISA. The polyclonal sera were mostly directed against antigen-combining site idiotopes and cross-reacted only with monoclonal anti-acetylcholine receptor antibodies that bound to the same region on the acetylcholine receptor. In contrast, five of the seven IgM monoclonal anti-idiotypic antibodies raised, none of which demonstrated antigen-combining site specificity in solution, cross-reacted with mAbs binding to more than one region. None of the antisera showing reactivity with the antigen-combining site inhibited the binding of MG anti-acetylcholine receptor antibody.
Roberts
A
A
Department of Clinical Neurology, John Radcliffe Hospital, Oxford.
Lang
B
B
Vincent
A
A
Newsom-Davis
J
J
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis*; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008807:Mice, Inbred BALB C; D009157:Myasthenia Gravis / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D011950:Receptors, Cholinergic