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

¹ Interstitial 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 Genetics and Genomics Section, Roche Pharmaceuticals, Nutley, NJ, USA
³ Department of Academic Rheumatology, Royal Free Hospital, London, UK

Correspondence to:
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.dubois{at}rbh.nthames.nhs.uk

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.

Abbreviations: ATA, antitopoisomerase antibody; EAE, experimental autoimmune encephalomyelitis; IL, interleukin; MHC, major histocompatibility complex; PHA, phytohaemagglutinin; PLP, proteolipid protein; SI, stimulation index; SSc, systemic sclerosis; TNF, tumour necrosis factor ; TT, tetanus toxoid

Keywords: scleroderma; autoantigen; topoisomerase I

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