Binding properties of immunoglobulin combining sites specific for terminal or nonterminal antigenic determinants in dextran.

Binding properties of immunoglobulin combining sites specific for terminal or nonterminal antigenic determinants in dextran.
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DOI:
10.1084/jem.142.2.435
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发表时间:
1975-08-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Liao J
Liao J
中科院分区:
其他
文献类型:
--
作者:
Cisar J;Kabat EA;Dorner MM;Liao J

文献摘要

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已经测定了右旋糖酐反应性BALB/c小鼠IgA骨髓瘤蛋白W3129和QUPC 52与异麦芽糖系列低聚糖和甲葡糖苷的结合常数。蛋白质W3129对异麦芽糖戊糖(IM5)具有最大的互补性(δ度= 7180 cal/mol),其55-60%的总结合能指向甲基甲葡糖苷。蛋白QUPC 52与异麦芽糖己糖(IM6)结合最大(δ f度= -5,340 cal/mol),对异麦芽糖三糖(IM3)的结合能约占其总结合能的70%,而对异麦芽糖(IM2)或甲葡糖苷的结合能最多仅为5%。蛋白W3129与高α(1产6)键的支链右旋糖酐沉淀,并与合成α(1产6)键的线性右旋糖酐反应,但不沉淀。蛋白qupc52沉淀支链和线性右旋糖酐。因此,蛋白W3129的免疫优势基团被甲基α -葡糖苷模拟,并且该蛋白仅在α(1)连接的葡聚糖链的末端非还原端发生反应。蛋白QUPC 52有一个免疫优势组,由IM3表达,而不是较小的寡糖,该蛋白可以在α(1产6)连接的葡聚糖链的非末端位置发生反应。线性右旋糖酐沉淀似乎是一个有效的,虽然不是定量分析抗右旋糖酐与非末端特异性。与支链和线性右旋糖酐的定量沉淀反应表明,α(1)产生6)特异性的人抗右旋糖酐是具有末端和非末端特异性的分子混合物,每种类型的比例在个体之间是不同的。兔抗IM3或IM6与牛血清白蛋白偶联的抗血清也含有对葡聚糖链具有非末端特异性的抗体,尽管很大一部分具有末端特异性。低分子量临床葡聚糖N-150N(等于60000)的反应更像线性葡聚糖,而不像它的母体天然支链葡聚糖B512。这被认为是由于临床葡聚糖N-150N中大量的非末端决定因子,而每个分子中功能性末端决定因子的数量非常少。了解异麦芽糖基链的末端和非末端特异性以及不同的免疫优势结构对理解右旋糖酐的免疫化学反应具有重要价值。此外,先前对果糖蛋白反应性小鼠骨髓瘤蛋白和人类抗levans(55,84)的某些研究结果也表明levan链具有末端和非末端特异性。
Binding constants of the dextran-reactive BALB/c mouse IgA myeloma proteins W3129 and QUPC 52 have been determined for each member of the isomaltose series of oligosaccharides and for methyl alphaDglucoside. Protein W3129 has maximum complementarity for isomaltopentaose (IM5) deltaf degrees = 7,180 cal/mol) with 55-60% of the total binding energy directed against methylalphaDglucoside. Protein QUPC 52 gives maximum binding with isomaltohexaose (IM6) (deltaF degrees = -5,340 cal/mol) and has about 70% of its total binding energy for isomaltotriose (IM3), but at most only 5% for isomaltose (IM2) or methyl alphaDglucoside. Protein W3129 precipitates with branched dextrans high in alpha (1 yields 6) linkages and reacts with but does not precipitate a synthetic alpha (1 yields 6)-linked linear dextran. Protein QUPC 52 precipitates both branched and linear dextrans. Thus, the immunodominant group for protein W3129 is mimicked by methyl alphaDglucoside and this protein reacts exclusively at the terminal nonreducing ends of alpha (1 yields 6)-linked dextran chains. Protein QUPC 52 has an immunodominant group which is expressed by IM3 but not smaller oligosaccharides and this protein can react at nonterminal locations along alpha (1 yields 6)- linked dextran chains.Precipitation of linear dextran seems to be a valid although not quantitative assay for antidextrans with nonterminal specificity. Quantitative precipitin reactions with branched and linear dextrans suggest that alpha (1 yields 6)-specific human antidextrans are mixtures of molecules having terminal and nonterminal specificities and that the fraction of each type can vary among individuals. Rabbit antisera against IM3 or IM6 coupled to bovine serum albumin also appear to contain antibodies with nonterminal specificity for dextran chains although a large fraction has terminal specificity. Low molecular weight clinical dextran N-150N (congruent to 60,000) reacted more like linear dextran than like its parent native-branched dextran B512. This is thought to result from an abundance of nonterminal determinants in clinical dextran N-150N but a very small number of functional terminal determinants per molecule. An appreciation of terminal and nonterminal specificities and of the different immunodominant structures in isomaltosyl chains has proven to be of a great value in understanding the immunochemical reactions of dextrans. Moreover, certain previous findings with fructosan-reactive mouse myeloma proteins and human antilevans (55, 84) also suggest terminal and nonterminal specificities for levan chains.