Human thyroperoxidase folds in one complex B-cell immunodominant region.
Human thyroperoxidase (TPO) ectodomain is successively made of myeloperoxidase-, complement control protein repeat-, and epidermal growth factor-like gene modules. However, the TPO immunodominant region targeted by autoantibodies from patients with an autoimmune thyroid disease has not been mapped on the molecule. Here, we used two purified recombinant TPO peptides produced in eukaryotic cells, which correspond to the major first and the further two gene modules of TPO. We compared by ELISA their respective immunoreactivity with that of the recombinant soluble TPO containing all the three gene modules. We used well-characterized murine and human TPO monoclonal antibodies and human autoantibodies affinity-purified from a large pool of patients' sera. We found that the TPO immunodominant region was susceptible to denaturation and required the integrity of the molecule to be correctly expressed. We concluded that TPO B-cell autoepitopes are made by amino acids from the three gene modules, which fold in one highly conformational immunodominant region.
U555 INSERM, Faculté de Médecine Timone, Université de la Méditerranée, 27 Boulevard Jean Moulin, F-13385 Marseille Cedex 5, France.
Stéphanie
S
Blanchin
Valérie
V
Estienne
Jin
J
Guo
Basil
B
Rapoport
Sandra M
SM
McLachlan
Pierre
P
Carayon
Jean
J
Ruf
D001402:B-Lymphocytes / Q000378:metabolism*; D001665:Binding Sites; D006801:Humans; D007453:Iodide Peroxidase / Q000737:chemistry* / Q000276:immunology; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology
D011994:Recombinant Proteins; D007453:Iodide Peroxidase