Polyspecific reactivity of a murine monoclonal antibody that binds to nuclear matrix-associated, chromatin-bound autoantigens.
To investigate polyspecific autoantibody interactions, we have characterized the binding of a cloned murine monoclonal IgM antibody termed (RTE-23) of strain BALB/c origin. By indirect immunofluorescence this antibody displayed a nuclear speckled and peripheral pattern in interphase cells from human and rodent cell lines. In contrast, in mitotic cells, antibody RTE-23 bound to the periphery of individual chromosomes. Immunoblot analysis of soluble and insoluble nuclear proteins from purified rat fibroblast nuclei showed that antibody RTE-23 bound to molecules of 28, 29, and 33 kDa. Furthermore, antibody RTE-23 demonstrated marked polyspecificity and reacted with cytoskeletal proteins (vimentin, keratin, actin), single-stranded DNA, specific synthetic polynucleotides, and cardiolipin. Antibody RTE-23 also showed a lupus anticoagulant-like activity. Screening of sera of autoimmune disease patients with antinuclear antibodies revealed two patients, both with SLE, whose sera blocked antibody RTE-23 binding to nuclei and recognized nuclear proteins identical to those recognized by antibody RTE-23. These results suggested that antibody RTE-23 displays a pattern of self-antigen binding that is represented as well in SLE patient sera.
Laster
A J
AJ
Pisetsky
D S
DS
Haynes
B F
BF
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001324:Autoantigens / Q000276:immunology*; D002308:Cardiolipins / Q000276:immunology; D002467:Cell Nucleus / Q000276:immunology* / Q000648:ultrastructure; D002843:Chromatin / Q000276:immunology*; D003593:Cytoplasm / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000276:immunology; D004247:DNA / Q000276:immunology; D005455:Fluorescent Antibody Technique; D007075:Immunoglobulin M / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008970:Molecular Weight; D010710:Phosphates / Q000276:immunology
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D002308:Cardiolipins; D002843:Chromatin; D003598:Cytoskeletal Proteins; D007075:Immunoglobulin M; D010710:Phosphates; D004247:DNA