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. 2004 Aug;63(8):982–987. doi: 10.1136/ard.2003.008037

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

S Veeraraghavan 1, E Renzoni 1, H Jeal 1, M Jones 1, J Hammer 1, A Wells 1, C Black 1, K Welsh 1, R M du Bois 1
PMCID: PMC1755092  PMID: 15249326

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.

Full Text

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Figure 1.

Figure 1

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 Dot histogram showing the average change in the number of counts per minute (Δcpm) for the proliferation assays to each of the peptides in controls (A) and patients with SSc (B). Filled circles show reactions with an SI >2.

Figure 2.

Figure 2

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 Significant correlation between disease duration and number of peptides inducing proliferation in patients with SSc.

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