Effector Functions of Camelid Heavy-Chain Antibodies in Immunity to West Nile Virus
Effector Functions of Camelid Heavy-Chain Antibodies in Immunity to West Nile Virus
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DOI：
10.1128/cvi.00421-09
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发表时间：
2010-02-01
影响因子：
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通讯作者：
Appleton, J. A.
中科院分区：
文献类型：
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作者：
Daley, L. P.;Kutzler, M. A.;Appleton, J. A.
骆驼科动物中有三类IgG。IgG 1具有常规的四链结构，而IgG 2和IgG 3不包含轻链。已详细研究了所谓重链类的结构和抗原结合亲和力;然而，它们的调节和效应子功能在很大程度上是不确定的。本研究的目的是检查常规和重链IgG抗体在骆驼免疫防御针对西尼罗河病毒（WNV）的参与。我们发现，自然感染或接种灭活的WNV诱导IgG 1和IgG 3。疫苗接种还诱导IgG 1和IgG 3; IgG 2在对疫苗接种的回忆反应期间产生。当在空斑减少中和滴度（PRNT）测试中测试纯化的IgG时，IgG 3表现出与常规IgG 1相当的PRNT活性。相比之下，IgG 2在测试的最高浓度下仅表现出次优活性。流式细胞术分析显示巨噬细胞结合IgG 1、IgG 2和IgG 3。此外，所有三种同种型的亚中和浓度增强了培养的巨噬细胞的WNV感染。我们的研究结果文件骆驼重链同种型之间的调节和功能的区别。IgG 3的减小的尺寸和独特的结构没有对其中和病毒的能力产生负面影响。相比之下，IgG 2似乎在中和中效率较低。这些信息推进了我们对这些不寻常抗体的理解，这些抗体可以应用于骆驼有效疫苗的开发。
Three classes of IgG have been described for camelids. IgG1 has a conventional four-chain structure, while IgG2 and IgG3 do not incorporate light chains. The structures and antigen-binding affinities of the so-called heavy-chain classes have been studied in detail; however, their regulation and effector functions are largely undefined. The aim of this study was to examine the participation of conventional and heavy-chain IgG antibodies in the camelid immune defense directed against West Nile virus (WNV). We found that natural infection or vaccination with killed WNV induced IgG1 and IgG3. Vaccination also induced IgG1 and IgG3; IgG2 was produced during the anamnestic response to vaccination. When purified IgGs were tested in plaque-reduction neutralization titer (PRNT) tests, IgG3 demonstrated PRNT activities comparable to those of conventional IgG1. In contrast, IgG2 demonstrated only suboptimal activity at the highest concentrations tested. Flow cytometric analysis revealed that macrophages bound IgG1, IgG2, and IgG3. Furthermore, subneutralizing concentrations of all three isotypes enhanced WNV infection of cultured macrophages. Our results document distinctions in regulation and function between camelid heavy-chain isotypes. The reduced size and distinct structure of IgG3 did not negatively impact its capacity to neutralize virus. In contrast, IgG2 appeared to be less efficient in neutralization. This information advances our understanding of these unusual antibodies in ways that can be applied in the development of effective vaccines for camelids.