Article Text
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
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Footnotes
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The work was done at the Royal Brompton Hospital, London, UK