ANTITOPOISOMERASE-I MONOCLONAL AUTOANTIBODIES FROM SCLERODERMA PATIENTS AND TIGHT SKIN MOUSE INTERACT WITH SIMILAR EPITOPES
- Author(s)
- MURYOI, T; KASTURI, KN; KAFINA, MJ; Cram, DS; Harrison, LC; SASAKI, T; BONA, CA;
- Details
- Publication Year 1992-04-01,Volume 175,Issue #4,Page 1103-1109
- Journal Title
- JOURNAL OF EXPERIMENTAL MEDICINE
- Publication Type
- Journal Article
- Abstract
- 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.
- Publisher
- ROCKEFELLER UNIV PRESS
- Keywords
- TOPOISOMERASE-I; ANTIGEN; SERA; AUTOIMMUNITY; ANTIBODIES; SCL-70; DNA
- Publisher's Version
- https://doi.org/10.1084/jem.175.4.1103
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1992-04-01 12:00:00