Human IgE mAbs identify major antigens of parasitic worm infection.
Human IgE mAbs identify major antigens of parasitic worm infection.
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DOI：
10.1016/j.jaci.2022.05.022
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发表时间：
2022-12
影响因子：
14.2
通讯作者：
Smith, Scott A.
中科院分区：
文献类型：
--
作者：
Hadadianpour, Azadeh;Daniel, Jacob;Zhang, Jian;Spiller, Benjamin W.;Makaraviciute, Asta;DeWitt, Asa M.;Walden, Heather S.;Hamilton, Robert G.;Peebles, R. Stokes, Jr.;Nutman, Thomas B.;Smith, Scott A.
我们对IgE靶点的了解大多来自过敏研究，尽管对寄生虫感染后的天然免疫原性靶点知之甚少。使用人单克隆抗体（mab）可以在与IgE水平升高相关的条件下（如过敏、蠕虫感染）对IgE靶向的免疫优势抗原进行公正、全面的表征。利用人杂交瘤技术，从丝虫病感染和IgE升高的受试者外周血中永生化编码IgE的b细胞，我们产生了天然存在的人IgE单克隆抗体。b细胞培养物以无偏倚的方式筛选IgE产生，而不考虑特异性。然后用免疫cap、免疫印迹和ELISA检测分离的IgE单抗与马来布鲁吉亚体细胞提取物（BmA）的结合。采用免疫沉淀法和质谱蛋白质组学技术鉴定蠕虫抗原，然后在大肠杆菌中表达以进行IgE结合鉴定。我们从7例丝虫病患者中分离出56个独立的IgE单抗。从这些单克隆抗体中，我们能够明确地鉴定出19种丝虫抗原。所有IgE单抗靶向丝虫排泄/分泌（E/S）蛋白，包括一个以前未表征的蛋白家族。有趣的是，转甲状腺素相关抗原是丝虫病特异性IgE抗体反应的主要诱导剂。这些丝虫病特异性IgE单抗在被动给药于表达hfcε ri的小鼠时是有效的过敏反应诱导剂。我们已经产生了人类杂交瘤，从丝虫病感染的受试者分泌自然发生的蠕虫特异性IgE单抗。这项工作为蠕虫诱导的免疫反应/IgE抗体反应的个体发生提供了急需的见解。这是首次描述在人寄生虫感染期间IgE抗体应答所针对的显性抗原。
Much of our understanding of the targets of IgE comes from studies of allergy, though little is known about the natural immunogenic targets seen following parasitic worm infections. The use of human monoclonal antibodies (mAbs) allow for an unbiased, comprehensive characterization of the immunodominant antigens targeted by IgE in conditions (e.g., allergy, helminth infection) associated with elevated levels of IgE. Using human hybridoma technology to immortalize IgE encoding B-cells from peripheral blood of subjects with filarial infections and elevated IgE, we generated naturally-occurring human IgE mAbs. B-cell cultures were screened in an unbiased manner for IgE production without regard to specificity. Isolated IgE mAbs then were tested for binding to Brugia malayi somatic extracts (BmA) using ImmunoCAP, immunoblot, and ELISA. Immunoprecipitation followed by mass spectrometry proteomics was used to identify helminth antigens that were then expressed in E. coli for IgE binding characterization. We isolated 56 discrete IgE mAbs from 7 individuals with filarial infections. From these mAbs, we were able to definitively identify 19 filarial antigens. All IgE mAbs targeted filarial excreted/secretory (E/S) proteins, including a family of previously uncharacterized proteins. Interestingly, the transthyretin-related antigens acted as the dominant inducer of the filaria-specific IgE antibody response. These filaria-specific IgE mAbs were potent inducers of anaphylaxis when passively administered to hFcεRI-expressing mice. We have generated human hybridomas secreting naturally-occurring helminth-specific IgE mAbs from filarial-infected subjects. This work provides much needed insights into the ontogeny of the helminth-induced immune response/IgE antibody response. This is the first description of the dominant antigens targeted by the IgE antibody response during human parasitic worm infection.
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DOI：
10.1111/nph.13701
发表时间：
2016-02
期刊：
The New phytologist
影响因子：
--
作者：
Lin B;Zhuo K;Chen S;Hu L;Sun L;Wang X;Zhang LH;Liao J
通讯作者：
Liao J
影响因子：
3.8
作者：
Flor Garcia-Mayoral, Maria;Angel Trevino, Miguel;Rodriguez-Perez, Rosa
通讯作者：
Rodriguez-Perez, Rosa
影响因子：
4.8
作者：
Bethony, J;Loukas, A;Hotez, PJ
通讯作者：
Hotez, PJ
影响因子：
--
作者：
FRIEDEMANN, U
通讯作者：
FRIEDEMANN, U
影响因子：
14.2
作者：
Homann, Arne;Schramm, Gabriele;Jappe, Uta
通讯作者：
Jappe, Uta