Monoclonal anti-acetylcholine receptor antibodies can cause experimental myasthenia

Abstract

Myasthenia gravis (MG) is a disease which occurs as a consequence of an autoimmune response directed against the nicotinic acetylcholine receptor (AChR) of the myoneural junction. Antisera raised against complex antigens such as AChR comprise a mixture of antibodies reactive with various determinants on the antigen molecule. The antibodies against any single determinant may be of several immunoglobulin classes and idiotypes. Antibodies produced by cloned lymphocyte-myeloma hybridoma cell lines have provided a way of analysing the diverse components making up a polyclonal antiserum and assessing the relative contribution made by each to the overall immune reaction in vivo. We have applied this technique to the investigation of the autoimmune response in MG. We demonstrate here that certain monoclonal anti-Torpedo AChR antibodies, when injected intravenously into normal rats, induce an acute myasthenic syndrome. Thus binding of a single molecular species of antibody reactive with a single antigenic determinant can result in all of the manifestations of an autoimmune disease.