Antitopoisomerase I monoclonal autoantibodies from scleroderma patients and tight skin mouse interact with similar epitopes.

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Muryoi, T; Kasturi, KN; Kafina, MJ; Cram, DS; Harrison, LC; Sasaki, T; Bona, CADate
1992-04-01Source Title
Journal of Experimental MedicinePublisher
Rockefeller University PressUniversity of Melbourne Author/s
Harrison, LeonardAffiliation
Medical Biology (W.E.H.I.)Metadata
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Muryoi, T., Kasturi, K. N., Kafina, M. J., Cram, D. S., Harrison, L. C., Sasaki, T. & Bona, C. A. (1992). Antitopoisomerase I monoclonal autoantibodies from scleroderma patients and tight skin mouse interact with similar epitopes.. J Exp Med, 175 (4), pp.1103-1109. https://doi.org/10.1084/jem.175.4.1103.Access Status
Open AccessOpen Access at PMC
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2119171Abstract
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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