IDENTIFICATION OF A UNIVERSAL B-CELL EPITOPE ON DNA TOPOISOMERASE-I, AN AUTOANTIGEN ASSOCIATED WITH SCLERODERMA

Objective. To investigate the distribution of B cell autoepitopes of h uman DNA topoisomerase I (topo I), an autoantigen associated with scle roderma. 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-t opo I-positive sera from patients with scleroderma, by immunoblotting, enzyme-linked immunosorbent assay, and double immunodiffusion. Result s. One epitope was found to be universally recognized by all sera test ed. Thirty-two of the samples recognized multiple antigenic regions, b ut sera from the remaining 3 patients recognized only this universal e pitope, and in longitudinal studies of 1 of these 3 patients, the seru m recognized only this epitope for more than 2 years, even though mult iple, potent, antigenic regions were found on topo I. Conclusion. Reco gnition of multiple epitopes in most patients suggests that the topo I molecule itself would drive the autoimmunity on topo I. However, anti gen-driven autoimmunity could not explain the production of the monore active anti-topo I antibody seen in the 3 patients. We thus hypothesiz e that there is a process whereby recognition of the universal epitope by cross-reaction develops into antigen-driven autoimmunity.