An immunodominant epitope on DNA topoisomerase I is conformational in nature: heterogeneity in its recognition by systemic sclerosis sera. Academic Article uri icon

Overview

abstract

  • OBJECTIVE: To characterize an immunodominant epitope recognized by anti-DNA topoisomerase I (topo I) antibody, a major autoantibody in sera of patients with systemic sclerosis (SSc). METHODS: Topo I fragments were generated as fusion proteins using a bacterial expression system as well as polypeptides translated in vitro using a eukaryotic expression system. Reactivities to the 2 preparations of recombinant topo I polypeptides in anti-topo I-positive sera from SSc patients of varied ethnic backgrounds were examined by immunoblotting, immunoprecipitation, and/or enzyme-linked immunosorbent assay. RESULTS: The fragment encoding amino acids 489-573 of topo I was recognized by 98 of 100 anti-topo I-positive SSc sera. Both carboxyl- and amino-terminal deletion studies as well as competitive inhibition assays using topo I synthetic peptides showed that a region of > or =52 amino acids (512-563) was necessary for recognition by anti-topo I antibodies. The minimum epitope region and conformation required for this reactivity were variable among sera from Caucasian, African American, Japanese, and Choctaw SSc patients. CONCLUSION: An immunodominant epitope recognized by anti-topo I autoantibody is located in the region of amino acids 489-573 of the topo I protein and is largely conformational in nature. The recognition pattern of this region by anti-topo I-positive sera is heterogeneous and is influenced by ethnic background.

publication date

  • June 1, 1999

Research

keywords

  • Autoantibodies
  • Autoantigens
  • DNA Topoisomerases, Type I
  • Immunodominant Epitopes
  • Scleroderma, Systemic

Identity

Scopus Document Identifier

  • 0033067817

Digital Object Identifier (DOI)

  • 10.1002/1529-0131(199906)42:6<1179::AID-ANR14>3.0.CO;2-E

PubMed ID

  • 10366110

Additional Document Info

volume

  • 42

issue

  • 6