We have generated for the first time monoclonal antibodies (mAbs) specific for topoisomerase I (topo I) from scleroderma patients, and tight skin mice which develop a scleroderma-like syndrome. The epitope specificity of these antibodies has been determined using a series of fusion proteins containing contiguous portions of topo I polypeptide. Western blot analysis demonstrated that both human and mouse mAbs bound strongly to fusion protein C encompassing the NH2-terminal portion of the enzyme, and weakly to fusion proteins F and G containing regions close to the COOH-terminal end of the molecule. This crossreactivity is related to a tripeptide sequence homology in F, G, and C fusion proteins. It is interesting that a pentapeptide sequence homologous to that in fusion protein C was identified in the UL70 protein of cytomegalovirus, suggesting that activation of autoreactive B cell clones by molecular mimicry is possible. Both human and mouse mAbs exhibiting the same antigen specificity, also share an interspecies cross-reactive idiotope. These data suggest that B cell clones producing antitopo autoantibodies present in human and mouse repertoire are conserved during phylogeny, and are activated during the development of scleroderma disease.
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1 April 1992
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April 01 1992
Antitopoisomerase I monoclonal autoantibodies from scleroderma patients and tight skin mouse interact with similar epitopes.
T Muryoi,
T Muryoi
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
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K N Kasturi,
K N Kasturi
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
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M J Kafina,
M J Kafina
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
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D S Cram,
D S Cram
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
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L C Harrison,
L C Harrison
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
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T Sasaki,
T Sasaki
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
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C A Bona
C A Bona
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
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T Muryoi
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
K N Kasturi
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
M J Kafina
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
D S Cram
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
L C Harrison
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
T Sasaki
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
C A Bona
Department of Microbiology, Mount Siani School of Medicine, New York, New York 10029-6574.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1992) 175 (4): 1103–1109.
Citation
T Muryoi, K N Kasturi, M J Kafina, D S Cram, L C Harrison, T Sasaki, C A Bona; Antitopoisomerase I monoclonal autoantibodies from scleroderma patients and tight skin mouse interact with similar epitopes.. J Exp Med 1 April 1992; 175 (4): 1103–1109. doi: https://doi.org/10.1084/jem.175.4.1103
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