02499nas a2200409 4500000000100000008004100001260001300042653001200055653002700067653002500094653003100119653002800150653002500178653002600203653002500229653003500254653001100289653001500300653002900315653001700344653002500361653002400386653000900410653002700419100001500446700002200461700001900483700002100502700001100523700001500534700001700549245016300566300001100729490000700740520132800747022001402075 1988 d c1988 Dec10aAnimals10aAntibodies, Monoclonal10aAntibody Specificity10aAntigen-Antibody Reactions10aBinding Sites, Antibody10aBinding, Competitive10aCytoskeletal Proteins10aDNA, Single-Stranded10aFluorescent Antibody Technique10aHumans10aHybridomas10aImmunoglobulin Idiotypes10aMitochondria10aMycobacterium leprae10aPolyribonucleotides10aRats10aReceptors, Cholinergic1 aDuggan D B1 aMackworth-Young C1 aKari-Lefvert A1 aAndre-Schwartz J1 aMudd D1 aMcAdam K P1 aSchwartz R S00aPolyspecificity of human monoclonal antibodies reactive with Mycobacterium leprae, mitochondria, ssDNA, cytoskeletal proteins, and the acetylcholine receptor. a327-400 v493 a

The origin of autoantibodies against ubiquitous autoantigens (e.g., single-stranded (SS) DNA, cytoskeletal proteins, mitochondria) is obscure. Patients with lepromatous leprosy have many such autoantibodies in their serum. In order to study the polyspecificities of human autoantibodies expressed during infection with Mycobacterium leprae we prepared human monoclonal antibodies derived from the fusion of peripheral blood lymphocytes of a patient with lepromatous leprosy to the human lymphoblastoid line GM 4672. Hybridomas were tested for binding to a DNAse-treated sonicate of M. leprae and a panel of autoantigens. Of the primary (uncloned) cultures, 14% bound ssDNA, 35% bound M. leprae, 11% bound both M. leprae and ssDNA, and 16% bound to mitochondria. Several also bound to the acetylcholine receptor of Torpedo marmorata. Monoclonal antibodies derived from separate primary cultures revealed similar cross-reactions between several autoantigens and M. leprae. In addition, one antibody was identified which bound to mitochondria and the acetylcholine receptor, and which was recognized by an anti-idiotypic antibody which bears the "internal image" of the acetylcholine receptor. These results suggest that antigenic mimicry may play a role in eliciting autoantibody expression from the immune repertoire.

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