title: Mapping of the immunodominant T cell epitopes of the protein topoisomerase I.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Occupational Medicine, National Heart and Lung Institute, Royal Brompton Hospital and Imperial College of Science Technology and Medicine, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Veeraraghavan
authors.forename: E A
authors.initials: EA
authors.lastname: Renzoni
authors.forename: H
authors.initials: H
authors.lastname: Jeal
authors.forename: M
authors.initials: M
authors.lastname: Jones
authors.forename: J
authors.initials: J
authors.lastname: Hammer
authors.forename: A U
authors.initials: AU
authors.lastname: Wells
authors.forename: C M
authors.initials: CM
authors.lastname: Black
authors.forename: K I
authors.initials: KI
authors.lastname: Welsh
authors.forename: R M
authors.initials: RM
authors.lastname: du Bois
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016207:Cytokines / Q000096:biosynthesis; D004264:DNA Topoisomerases, Type I / Q000276:immunology*; D018604:Epitope Mapping / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000032:analysis*; D005260:Female; D006681:HLA-D Antigens / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D016056:Immunodominant Epitopes / Q000032:analysis*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006681:HLA-D Antigens; D016056:Immunodominant Epitopes; D009842:Oligopeptides; D004264:DNA Topoisomerases, Type I