Polyspecificity of human monoclonal antibodies reactive with Mycobacterium leprae, mitochondria, ssDNA, cytoskeletal proteins, and the acetylcholine receptor.
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.
Duggan
D B
DB
Department of Medicine, Tufts-New England Medical Center, Boston, Massachusetts.
Mackworth-Young
C
C
Kari-Lefvert
A
A
Andre-Schwartz
J
J
Mudd
D
D
McAdam
K P
KP
Schwartz
R S
RS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology; D000918:Antibody Specificity; D000937:Antigen-Antibody Reactions; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D003598:Cytoskeletal Proteins / Q000276:immunology*; D004277:DNA, Single-Stranded / Q000276:immunology* / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D006825:Hybridomas / Q000378:metabolism; D007130:Immunoglobulin Idiotypes / Q000378:metabolism; D008928:Mitochondria / Q000276:immunology*; D009166:Mycobacterium leprae / Q000276:immunology* / Q000502:physiology; D011131:Polyribonucleotides / Q000494:pharmacology; D051381:Rats; D011950:Receptors, Cholinergic / Q000276:immunology* / Q000378:metabolism
D000911:Antibodies, Monoclonal; D003598:Cytoskeletal Proteins; D004277:DNA, Single-Stranded; D007130:Immunoglobulin Idiotypes; D011131:Polyribonucleotides; D011950:Receptors, Cholinergic