Rebuffat Sandra A, Bresson Damien, Nguyen Brigitte, Péraldi-Roux Sylvie
CNRS UMR 5160, Faculté de Pharmacie, 34093 Montpellier Cedex 5, France.
Int Immunol. 2006 Jul;18(7):1091-9. doi: 10.1093/intimm/dxl042. Epub 2006 May 30.
Auto-antibodies (aAbs) to thyroid peroxidase (TPO) interact with a restricted immunodominant region (IDR) divided into two overlapping regions A and B. Among the five major regions structuring the IDR/B, regions 210-225, 353-363, 549-563, 713-720 and 766-775, region 353-363 constitutes an important anchor point for the binding of TPO-specific aAbs in sera from Hashimoto's and Graves' patients. We combined site-directed mutagenesis and expression of TPO mutants in stably transfected CHO cells to precisely define the critical residues in that region. By using flow cytometry and ELISA, we identified four amino acid residues, H353, D358, S359 and R361, that contribute to the interaction between human TPO and anti-TPO aAbs. This identification of these contributing amino acid residues in the IDR allowed us to more precisely depict contours of the IDR.
甲状腺过氧化物酶(TPO)自身抗体(aAbs)与一个受限的免疫显性区域(IDR)相互作用,该区域分为两个重叠区域A和B。在构成IDR/B的五个主要区域中,即210 - 225、353 - 363、549 - 563、713 - 720和766 - 775区域,353 - 363区域是桥本氏病和格雷夫斯病患者血清中TPO特异性aAbs结合的重要锚定点。我们将定点诱变与TPO突变体在稳定转染的CHO细胞中的表达相结合,以精确确定该区域中的关键残基。通过流式细胞术和酶联免疫吸附测定(ELISA),我们鉴定出四个氨基酸残基H353、D358、S359和R361,它们有助于人TPO与抗TPO aAbs之间的相互作用。对IDR中这些起作用的氨基酸残基的鉴定使我们能够更精确地描绘IDR的轮廓。