Related Experiment Videos
Identification of a universal B cell epitope on DNA topoisomerase I, an autoantigen associated with scleroderma
T Kato1, K Yamamoto, H Takeuchi
1Institute of Medical Science, St. Marianna University School of Medicine, Kanagawa, Japan.
Objective:
To investigate the distribution of B cell autoepitopes of human DNA topoisomerase I (topo I), an autoantigen associated with scleroderma.
Methods:
A complementary DNA clone, T1B, was used to produce recombinant proteins of topo I as beta-galactosidase fusion proteins. Immunoreactivity to these fusion proteins was then tested in 35 anti-topo I-positive sera from patients with scleroderma, by immunoblotting, enzyme-linked immunosorbent assay, and double immunodiffusion.
Results:
One epitope was found to be universally recognized by all sera tested. Thirty-two of the samples recognized multiple antigenic regions, but sera from the remaining 3 patients recognized only this universal epitope, and in longitudinal studies of 1 of these 3 patients, the serum recognized only this epitope for more than 2 years, even though multiple, potent, antigenic regions were found on topo I.
Conclusion:
Recognition of multiple epitopes in most patients suggests that the topo I molecule itself would drive the autoimmunity on topo I. However, antigen-driven autoimmunity could not explain the production of the monoreactive anti-topo I antibody seen in the 3 patients. We thus hypothesize that there is a process whereby recognition of the universal epitope by cross-reaction develops into antigen-driven autoimmunity.