Mapping of the immunodominant T cell epitopes of the protein topoisomerase I

Ann Rheum Dis. 2004 Aug;63(8):982-7. doi: 10.1136/ard.2003.008037.

Abstract

Objectives: To identify the immunodominant T cell epitopes of the topoisomerase I protein in patients with systemic sclerosis (SSc) and control subjects, using computational analysis software (TEPITOPE) and T cell proliferation assays.

Methods: Six oligopeptides, predicted by TEPITOPE software as potential topoisomerase protein epitopes, were used to perform T cell proliferation assays in 21 patients with SSc and 15 healthy controls.

Results: A positive response to at least one of the peptides was seen in 10/21 patients and 7/15 healthy controls. Among responders, the proliferative response was limited to a single peptide in 6/7 healthy controls, whereas 5/10 patients responded to more than one peptide. In responding patients a significant correlation was found between disease duration and number of peptides inducing a response (p = 0.007).

Conclusions: Several T cell epitopes of the topoisomerase I protein have been identified and evidence has been found to suggest epitope spreading in patients with SSc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Cytokines / biosynthesis
  • DNA Topoisomerases, Type I / immunology*
  • Epitope Mapping / methods
  • Epitopes, T-Lymphocyte / analysis*
  • Female
  • HLA-D Antigens / genetics
  • Histocompatibility Testing
  • Humans
  • Immunodominant Epitopes / analysis*
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Oligopeptides / immunology
  • Scleroderma, Systemic / immunology*
  • T-Lymphocytes / immunology

Substances

  • Cytokines
  • Epitopes, T-Lymphocyte
  • HLA-D Antigens
  • Immunodominant Epitopes
  • Oligopeptides
  • DNA Topoisomerases, Type I