Exploring binding and effector functions of natural human antibodies using synthetic immunomodulators.
Exploring binding and effector functions of natural human antibodies using synthetic immunomodulators.
复制标题
DOI：
10.1021/cb4004942
复制
发表时间：
2013-11-15
影响因子：
4
通讯作者：
Spiegel, David A.
中科院分区：
文献类型：
--
作者：
Jakobsche, Charles E.;Parker, Christopher G.;Tao, Ran N.;Kolesnikova, Mariya D.;Douglass, Eugene F., Jr.;Spiegel, David A.
分析内源性抗体的流行和功能活性的能力具有巨大的临床和诊断重要性。血清抗体是一类重要的生物标志物，也是自然致病因子和疫苗引起的免疫反应的关键因素。特别是，用于操纵和/或增强对致病细胞或病毒的免疫反应的材料已显示出治疗应用的重大前景。抗体招募分子（ARMs）是一种双功能有机分子，可将内源性抗体重新定向到病理靶点，从而增加免疫系统对其的识别和清除，已被证明特别有趣。值得注意的是，尽管arm能够劫持针对寡糖和电子贫芳烃的抗体已被证明是有效的，但对天然抗半抗原抗体群体的患病率和有效性的系统比较尚未出现在文献中。在这里，我们报告头对头比较三种化学简单的抗原，这是已知的内源性抗体的配体。因此，我们化学合成了含有2,4-二硝基苯（DNP）、磷胆碱（PC）和鼠李糖的双功能分子。然后，我们结合ELISA、流式细胞术和细胞活力测定来比较这些抗原从人血清中招募天然抗体的能力，以及直接对靶细胞产生血清依赖性细胞毒性的能力。这些研究表明鼠李糖是所检测的合成抗原中最有效的。此外，对122个个体血清样本的分析提供了对不同的抗半抗原抗体群体的人群患病率和同型分布的全面见解。这些研究除了为比较和研究抗半抗原抗体提供了一个通用的平台外，还为优化抗体招募分子和其他调节人类免疫的合成策略提供了一个有用的起点。
The ability to profile the prevalence and functional activity of endogenous antibodies is of vast clinical and diagnostic importance. Serum antibodies are an important class of biomarkers and are also crucial elements of immune responses elicited by natural disease causing-agents as well as vaccines. In particular, materials for manipulating and/or enhancing immune responses toward disease-causing cells or viruses have exhibited significant promise for therapeutic applications. Antibody-recruiting molecules (ARMs) – bifunctional organic molecules that re-direct endogenous antibodies to pathological targets, thereby increasing their recognition and clearance by the immune system – have proven particularly interesting. Notably, although ARMs capable of hijacking antibodies against oligosaccharides and electron-poor aromatics have proven efficacious, systematic comparisons of the prevalence and effectiveness of natural anti-hapten antibody populations have not appeared in the literature. Herein we report head-to-head comparisons of three chemically-simple antigens, which are known ligands for endogenous antibodies. Thus, we have chemically synthesized bifunctional molecules containing 2,4-dinitrophenyl (DNP), phosphorylcholine (PC) and rhamnose. We then used a combination of ELISA, flow cytometry, and cell-viability assays to compare these antigens in terms of their abilities both to recruit natural antibody from human serum and also to direct serum-dependent cytotoxicity against target cells. These studies have revealed rhamnose to be the most efficacious of the synthetic antigens examined. Furthermore, analysis of 122 individual serum samples has afforded comprehensive insights into population-wide prevalence and isotype distributions of distinct anti-hapten antibody populations. In addition to providing a general platform for comparing and studying anti-hapten antibodies, these studies serve as a useful starting point for the optimization of antibody-recruiting molecules and other synthetic strategies for modulating human immunity.
登录
查看更多内容
与凋亡相关决定因素的IgM抗体募集C1Q并增强凋亡细胞的树突状细胞吞噬作用。
DOI：
10.4049/jimmunol.0804191
发表时间：
2009-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Chen Y;Park YB;Patel E;Silverman GJ
通讯作者：
Silverman GJ
影响因子：
5.4
作者：
KARJALAINEN, K;MAKELA, O
通讯作者：
MAKELA, O
影响因子：
3.2
作者：
Naicker, KP;Li, HG;Wang, LX
通讯作者：
Wang, LX
影响因子：
2.2
作者：
Lock, RJ;Unsworth, DJ
通讯作者：
Unsworth, DJ
影响因子：
8.3
作者：
Fiskesund, Roland;Stegmayr, Birgitta;Frostegard, Johan
通讯作者：
Frostegard, Johan