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单个氨基酸替换导致抗体独特型发生剧烈变化,但抗原结合特异性未变。

Drastic change in idiotypic but not antigen-binding specificity of an antibody by a single amino-acid substitution.

作者信息

Radbruch A, Zaiss S, Kappen C, Brüggemann M, Beyreuther K, Rajewsky K

出版信息

Nature. 1985;315(6019):506-8. doi: 10.1038/315506a0.

DOI:10.1038/315506a0
PMID:2582273
Abstract

In proliferating B lymphocytes, somatic mutation of rearranged antibody variable (V)-region genes occurs at high frequency and may have a key role in the selection of these cells. It is of interest in this context to learn in which way single mutations can affect antigen binding and/or idiotypic specificity of an antibody. Previous investigations have analysed spontaneous mutants of myeloma and hybridoma cells in which the mutation affected the antigen-binding specificity of the antibody. Here we describe an antibody mutant that has fully retained antigen-binding specificity but has lost or drastically changed all V-region antigenic determinants (idiotopes) of the wild type as defined by monoclonal anti-idiotope antibodies. The mutant phenotype is generated by a glycine to arginine exchange in the middle of the diversity (D) element, at position 103 of the heavy chain.

摘要

在增殖的B淋巴细胞中,重排的抗体可变(V)区基因的体细胞突变高频发生,并且可能在这些细胞的选择中起关键作用。在这种情况下,了解单个突变如何影响抗体的抗原结合和/或独特型特异性是很有意义的。先前的研究分析了骨髓瘤和杂交瘤细胞的自发突变体,其中突变影响了抗体的抗原结合特异性。在这里,我们描述了一种抗体突变体,它完全保留了抗原结合特异性,但失去或显著改变了野生型的所有V区抗原决定簇(独特型),这是由单克隆抗独特型抗体定义的。突变表型是由重链第103位多样性(D)元件中间的甘氨酸到精氨酸交换产生的。

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Nature. 1985;315(6019):506-8. doi: 10.1038/315506a0.
2
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引用本文的文献

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Rheumatol Int. 1994;13(5):187-96. doi: 10.1007/BF00390266.
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Rheumatoid factors from the peripheral blood of two patients with rheumatoid arthritis are genetically heterogeneous and somatically mutated.两名类风湿性关节炎患者外周血中的类风湿因子在基因上是异质的,且存在体细胞突变。
J Clin Invest. 1994 Feb;93(2):852-61. doi: 10.1172/JCI117040.
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The idiotypic network and the internal image: possible regulation of a germ-line network by paucigene encoded Ab2 (anti-idiotypic) antibodies in the GAT system.
独特型网络与内影像:在GAT系统中,寡基因编码的Ab2(抗独特型)抗体对种系网络的可能调控。
EMBO J. 1985 Dec 30;4(13B):3681-8. doi: 10.1002/j.1460-2075.1985.tb04135.x.
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Crossreactivity and inheritance of idiotypes restricted to human anti-tetanus toxoid antibodies.局限于人类抗破伤风类毒素抗体的独特型的交叉反应性与遗传性。
J Clin Invest. 1987 Apr;79(4):1242-8. doi: 10.1172/JCI112943.
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