Mapping of the immunodominant T cell epitopes of the protein topoisomerase I.
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.
Veeraraghavan
S
S
Department of Occupational Medicine, National Heart and Lung Institute, Royal Brompton Hospital and Imperial College of Science Technology and Medicine, London, UK.
Renzoni
E A
EA
Jeal
H
H
Jones
M
M
Hammer
J
J
Wells
A U
AU
Black
C M
CM
Welsh
K I
KI
du Bois
R M
RM
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
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006681:HLA-D Antigens; D016056:Immunodominant Epitopes; D009842:Oligopeptides; D004264:DNA Topoisomerases, Type I