Characterization of human anti-acetylcholine receptor monoclonal autoantibodies from the peripheral blood of a myasthenia gravis patient using combinatorial libraries

Myasthenia gravis (MG) is an autoimmune disease caused by autoantibodies ag ainst the nicotinic acetylcholine receptor (AChR), Using phage-display tech nology we have characterized the largest panel of anti-AChR monoclonal anti bodies thus far isolated from a single patient. Despite having been isolate d with either Torpedo AChR or a human peptide, the recombinant antibodies s hared with the donor's serum the ability to recognize human AChR expressed in its native configuration on the surface of TE671 cells. Their specificit y for the main immunogenic region (MIF) of the AChR was demonstrated using a synthetic peptide corresponding to the region 67-76 of the human AChR alp ha subunit and by inhibition of a highly pathogenic rat anti-MIR monoclonal antibody (mAb35), This work demonstrates the value of combinatorial librar ies in isolating pathogenic autoantibodies from peripheral blood lymphocyte s, Future genetic, structural, and functional analyses of the monoclonal an tibodies reported herein should enhance our understanding of the pathogenes is of MG. (C) 2000 Academic Press.