Recognition by recombinant autoimmune thyroid disease-derived Fab fragments of a dominant conformational epitope on human thyroid peroxidase.

Recognition by recombinant autoimmune thyroid disease-derived Fab fragments of a dominant conformational epitope on human thyroid peroxidase.
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通过重组自身免疫性甲状腺疾病衍生的 Fab 片段识别人甲状腺过氧化物酶上的显性构象表位。

DOI:
10.1172/jci115943
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发表时间:
1992
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
McLachlan,SM
McLachlan,SM
中科院分区:
--
文献类型:
--
作者:
Portolano,S;Chazenbalk,GD;Seto,P;Hutchison,JS;Rapoport,B;McLachlan,SM

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为了表征自身免疫性甲状腺疾病患者血清中存在的甲状腺过氧化物酶 (TPO) 自身抗体的性质,我们克隆了三个结合 125I-TPO 的 IgG1/kappa Fab 片段。这是通过对格雷夫斯病患者甲状腺浸润 B 细胞的 IgG 基因片段进行分子克隆并在细菌中表达来实现的。三个 Fab 片段(SP2、SP4 和 SP5)由共同的重链(VH1、D、JH3)和三个相关但不同的轻链(VK1、JK2)编码。 SP Fab 片段以与血清 TPO 自身抗体相当的高亲和力 (6 x 10(-11)-2 x 10(-10) M)特异性结合 TPO。以 SP Fab 片段为代表的 TPO 自身抗体存在于所研究的所有 11 名患者中,构成个体患者血清 TPO 自身抗体的高比例 (36-72%),并与 TPO 上的构象表位相互作用。
To characterize the nature of thyroid peroxidase (TPO) autoantibodies present in the sera of patients with autoimmune thyroid disease, we cloned three IgG1/kappa Fab fragments which bind 125I-TPO. This was accomplished by the molecular cloning and expression in bacteria of IgG gene fragments from B cells infiltrating the thyroid of a patient with Graves' disease. The three Fab fragments (SP2, SP4, and SP5) are coded for by a common heavy chain (VH1, D, JH3) and three related, but different, light chains (VK1, JK2). The SP Fab fragments bind specifically to TPO with high affinities (6 x 10(-11)-2 x 10(-10) M) comparable to those of serum TPO autoantibodies. TPO autoantibodies represented by the SP Fab fragments are present in all 11 patients studied, constitute a high proportion (36-72%) of serum TPO autoantibodies in individual patients and interact with a conformational epitope on TPO.
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