Camelid immunoglobulins and nanobody technology

Camelid immunoglobulins and nanobody technology
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DOI:
10.1016/j.vetimm.2008.10.299
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发表时间:
2009-03-15
影响因子:
1.8
通讯作者:
Saerens, D.
Saerens, D.
中科院分区:
农林科学3区
文献类型:
--
作者:
Muyldermans, S.;Baral, T. N.;Saerens, D.

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众所周知,所有骆驼科动物的血液中都有独特的抗体。与其他物种的抗体不同,这些特殊抗体缺乏轻链,由重链同源二聚体组成。这些所谓的重链抗体(HCAb)在V-D-J重排后表达,需要专用的恒定γ基因。按照经典免疫方案,在这些所谓的重链抗体中产生免疫应答。这些HCAb很容易从血清中纯化,抗原结合片段与对常规抗体抗原性较低的靶标部分相互作用。由于单峰骆驼HCAb的抗原结合位点包含在一个单一结构域中。称为HCAb重链可变区(VHH)或纳米抗体(Nb),我们设计了一种策略来克隆免疫单峰骆驼的Nb库并选择对我们的靶抗原具有特异性的Nbs。单克隆Nbs在细菌中充分产生,非常稳定且高度可溶,并且以高亲和力和特异性结合其同源抗原。我们已成功开发出用于研究目的的重组Nbs,作为生物传感器中的探针,用于诊断感染以及治疗癌症或锥虫病等疾病。(C)2008 Elsevier B. V.保留所有权利。
It is well established that all camelids have unique antibodies circulating in their blood. Unlike antibodies from other species, these special antibodies are devoid of light chains and are composed of a heavy-chain homodimer.These so-called heavy-chain antibodies (HCAbs) are expressed after a V-D-J rearrangement and require dedicated constant gamma-genes. An immune response is raised in these so-called heavy-chain antibodies following classical immunization protocols. These HCAbs are easily purified from serum, and the antigen-binding fragment interacts with parts of the target that are less antigenic to conventional antibodies. Since the antigen-binding site of the dromedary HCAb is comprised in one single domain. referred to as variable domain of heavy chain of HCAb (VHH) or nanobody (Nb), we designed a strategy to clone the Nb repertoire of an immunized dromedary and to select the Nbs with specificity for our target antigens. The monoclonal Nbs are well produced in bacteria, are very stable and highly soluble, and bind their cognate antigen with high affinity and specificity. We have successfully developed recombinant Nbs for research purposes, as probe in biosensors, to diagnose infections, and to treat diseases like cancer or trypanosomosis. (C) 2008 Elsevier B.V. All rights reserved.