NUCLEOTIDE-SEQUENCES OF VARIABLE REGIONS OF AN HUMAN ANTIACETYLCHOLINE RECEPTOR AUTOANTIBODY DERIVED FROM A MYASTHENIC PATIENT

Autoantibodies against the acetylcholine receptor (AChR) are involved in the neuromuscular dysfunction associated with myasthenia gravis (MG ). We determined the nucleotide and the deduced amino acid sequences o f the heavy and light chains for one human monoclonal anti-AChR autoan tibody, derived from peripheral blood lymphocytes obtained from one MG patient. The heavy and light chain (V-H and V-lambda) genetic element s used in this autoantibody are respectively or closely related to HHG 19 and Humlv117 germline structure. In addition, the expressed J(H), J (lambda) and D segments differ from their described germline structure s. This diversity could reflect allelic variation. The large number of differences found in V-H, V-L, and D genetic elements when compared w ith their most closely related germline structures allowed us to concl ude that we have characterized new V-H and V-L genes and we could not identify univocally somatic mutations. However, the analysed autoantib ody, an IgG specific for the alpha chain of the AChR, revealed the pre sence of N addition segments on both sides of the D region and we may postulate that this antibody was the result of an antigen driven pheno menon.