Antitopoisomerase I monoclonal autoantibodies from scleroderma patients and tight skin mouse interact with similar epitopes
| Autor: | Constantin A. Bona, Tai Muryoi, Kuppuswamy N. Kasturi, Leonard C. Harrison, David S. Cram, T Sasaki, M J Kafina |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
medicine.drug_class
Recombinant Fusion Proteins Blotting Western Molecular Sequence Data Immunology medicine.disease_cause Monoclonal antibody Autoantigens Epitope Autoimmune Diseases Epitopes Mice Western blot Antigen Antibody Specificity medicine Animals Immunology and Allergy Amino Acid Sequence Peptide sequence Autoantibodies Scleroderma Systemic biology medicine.diagnostic_test Antibodies Monoclonal Articles Fusion protein Molecular biology Mice Mutant Strains Molecular mimicry DNA Topoisomerases Type I biology.protein Antibody |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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