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J Biol Chem, Vol. 274, Issue 50, 35313-35317, December 10, 1999
From the While studying the humoral mechanisms involved in
thyroid autoimmunity, we located a B-cell autoepitope in the
extracellular C-terminal region of human thyroperoxidase. Structural
modeling showed that this region encompasses both a Sushi-like and an
epidermal growth factor-like domain, the flexible arrangement of which
was putatively stabilized by calcium. The recombinant peptide was found
to contain the previously identified conformational thyroperoxidase autoepitope. The occurrence of a calcium-induced conformational change
was confirmed using a recombinant peptide monoclonal antibody, the
decrease of which in binding to calcium-saturated thyroperoxidase was
reversed by a chelating agent. The disease specificity of recombinant
peptide, which was more frequently recognized by Hashimoto's than by
Graves' patients, adds to its potential value as a diagnostic and
preventive tool in the context of B-cell autoimmunity.
Molecular Model, Calcium Sensitivity, and Disease Specificity of
a Conformational Thyroperoxidase B-cell Epitope*
,,,,, and
U 38 INSERM/Laboratoire de Biochimie
Endocrinienne et Métabolique, Faculté de Médecine
Timone, Université de la Méditerranée, 13385 Marseille Cedex 05, France, the § Pôle de
Bioinformatique Lyonnais, IBCP-CNRS UPR 412, 69367 Lyon Cedex 07, France, and the ¶ Laboratoire d'Ingénierie des
Systèmes Macromoléculaires, IBSM, CNRS,
13402 Marseille Cedex 20, France
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence and requests for reprints should
be addressed: U38 INSERM, Faculté de Médecine Timone, 27 boulevard Jean Moulin, F-13385 Marseille Cedex 5, France. Tel.: +33
(0)4 91 32 43 82; Fax: +33 (0)4 91 79 77 74; E-mail:
Jean.Ruf@medecine.univ-mrs.fr.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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