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Extended report
Mapping of the immunodominant T cell epitopes of the protein topoisomerase I
  1. S Veeraraghavan1,
  2. E A Renzoni1,
  3. H Jeal1,
  4. M Jones1,
  5. J Hammer2,
  6. A U Wells1,
  7. C M Black3,
  8. K I Welsh1,
  9. R M du Bois1
  1. 1Interstitial Lung Disease Unit, Department of Occupational Medicine, National Heart and Lung Institute, Royal Brompton Hospital and Imperial College of Science Technology and Medicine, London, UK
  2. 2Genetics and Genomics Section, Roche Pharmaceuticals, Nutley, NJ, USA
  3. 3Department of Academic Rheumatology, Royal Free Hospital, London, UK
  1. Correspondence to:
    Professor R M du Bois
    Interstitial Lung Disease Unit, National Heart and Lung Institute, Royal Brompton Hospital, 1B Manresa road, London SW3 6LR, UK; r.duboisrbh.nthames.nhs.uk

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.

  • ATA, antitopoisomerase antibody
  • EAE, experimental autoimmune encephalomyelitis
  • IL, interleukin
  • MHC, major histocompatibility complex
  • PHA, phytohaemagglutinin
  • PLP, proteolipid protein
  • SI, stimulation index
  • SSc, systemic sclerosis
  • TNFα, tumour necrosis factor α
  • TT, tetanus toxoid
  • scleroderma
  • autoantigen
  • topoisomerase I

https://doi.org/10.1136/ard.2003.008037

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    Footnotes

    • The work was done at the Royal Brompton Hospital, London, UK