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诱导人分泌型免疫球蛋白 A 抗体的多特异性:提高其结合病原体的能力是否可行?

Induced Polyspecificity of Human Secretory Immunoglobulin A Antibodies: Is It Possible to Improve Their Ability to Bind Pathogens?

机构信息

Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod, Russian Federation.

Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, Sofia, Bulgaria.

出版信息

Pharmacology. 2022;107(7-8):341-350. doi: 10.1159/000520343. Epub 2021 Dec 3.

DOI:10.1159/000520343
PMID:34864734
Abstract

INTRODUCTION

As has been shown previously, various protein-modifying agents can change the antigen-binding properties of immunoglobulins. However, induced polyspecificity of human secretory immunoglobulin A (sIgA) has not been previously characterized in detail.

METHODS

In the present study, human secretory immunoglobulin A (IgA) was exposed to buffers with acidic pH, to free heme, or to pro-oxidative ferrous ions, and the antigen-binding behavior of the native and modified IgA to viral and bacterial antigens was compared using Western blotting and enzyme-linked immunosorbent assay. The ability of these agents to modulate the antigen-binding properties of human sIgA toward a wide range of pathogen peptides was investigated using an epitope microarray.

RESULTS

We have shown that acidic pH, heme, and pro-oxidative ferrous ions influenced the binding of secretory IgA in opposite directions (either increasing or decreasing); however, the strongest effect was observed when using buffers with low pH. This fraction had the highest number of affected reactivities; most of them were increased and most of the new ones were toward common pathogens.

CONCLUSIONS

Thus, it was shown that all investigated treatments can alter to some degree the antigen-binding of secretory IgA, but acidic pH has the most potentially beneficial effect by increasing binding to a largest number of common pathogens' antigens.

摘要

简介

如前所述,各种蛋白质修饰剂可以改变免疫球蛋白的抗原结合特性。然而,人类分泌型免疫球蛋白 A(sIgA)的诱导多特异性以前尚未详细描述。

方法

在本研究中,将人分泌型免疫球蛋白 A(IgA)暴露于 pH 值较低的缓冲液、游离血红素或促氧化亚铁离子中,并使用 Western blot 和酶联免疫吸附试验比较天然和修饰的 IgA 对病毒和细菌抗原的抗原结合行为。使用表位微阵列研究这些试剂对人 sIgA 针对广泛的病原体肽的抗原结合特性的调节能力。

结果

我们已经表明,酸性 pH 值、血红素和促氧化亚铁离子以相反的方向影响分泌型 IgA 的结合(要么增加要么减少);然而,当使用 pH 值较低的缓冲液时,观察到的效果最强。该部分具有最高数量的受影响的反应性;大多数是增加的,大多数新的是针对常见病原体的。

结论

因此,研究表明,所有研究的处理方法都可以在一定程度上改变分泌型 IgA 的抗原结合,但酸性 pH 值通过增加与大量常见病原体抗原的结合具有最潜在的有益效果。

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