Thyroglobulin monoclonal antibody cross-reacting with thyroperoxidase induces in syngeneic mice anti-idiotypic monoclonal antibodies with dual autoantigen binding properties. The intertope hypothesis
✍ Scribed by Christine Duthoit; Valérie Estienne; Josée-Martine Durand-Gorde; Pierre Carayon; Jean Ruf
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 137 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Autoimmune thyroid diseases are characterized by antibodies (Ab) directed to thyroglobulin (Tg) and thyroperoxidase (TPO). Some of them, TGPO Ab, are Tg Ab with an interspecies idiotype (Id) reacting with TPO. Taking advantage of a carefully studied TGPO monoclonal antibody (mAb), we examined the basis of the hypothesis that TPO Ab would ultimately derive from TGPO Ab through idiotypic induction. We repeatedly immunized naive, syngeneic mice with the TGPO mAb and we derived three novel mAb directed to both Tg and TPO. The most reactive of them, mAb 4F8, was further purified, radiolabeled and its binding properties studied by radioimmunoassay. mAb 4F8 bound to Tg, TPO, the immunogen Ab 1 and even to itself, being thus considered as a self-binding Ab 2 . Competitive binding inhibition experiments demonstrated that Tg, TPO, Ab 1 and Ab 2 cross-reacted for Ab 2 binding to Tg, TPO and Ab 1 . Fine specificity mapping using panels of specific mAb revealed that Ab 1 and Ab 2 were similar because they were directed against the same immunodominant regions on Tg and TPO. We propose that unique Id of TGPO Ab resemble dominant epitopes of Tg as well as paratopes of Ab directed against dominant TPO epitopes. This category of Id that we called intertopes may induce TPO-monospecific Ab from TGPO Ab by idiotypically driven somatic mutations.