抗体能进入细胞发挥免疫杀伤作用

来自马里兰大学，中国农业大学，加州理工学院的研究人员发表了题为“Intracellular neutralization of viral infection in polarized epithelial cells by neonatal Fc receptor (FcRn)-mediated IgG transport”的文章，提出了抗体对抗细胞内病毒的一种新方法：借助一种称为新生儿Fc受体（Neonatal Fc receptor, FcRn）的免疫蛋白，抗体能进入被感染的细胞发挥作用。这一研究成果公布在《美国国家科学院院刊》（PNAS）杂志上。

领导这项研究的是马里兰大学华裔科学家朱小平博士，朱小平研究组主要从事病毒分子免疫机制相关领域的研究，曾获得过许多这方面的新成果，发表PNAS，Nature Biotechnology等多篇文章。文章的另外一位通讯作者是来自加州理工学院的Pamela J. Björkmanc。

流感病毒能感染呼吸道上皮细胞表面，一旦进入细胞，这些病毒就会袭击遗传信息载体：DNA，拷贝自己的RNA，产生更多的病毒。IgG是抵御病毒的主要防线，能通过人体免疫系统对抗病毒，防止病毒引发疾病。

在这篇文章中，研究人员提出了一种流感血凝素特异性单克隆抗体：Y8-10C2（Y8）的细胞内对抗病毒的新机制，这种抗体只有在酸性环境下才具有对抗病毒的活性，研究人员发现了这一抗体作用活性需要利用新生儿Fc受体FcRn，通过FcRn的协同作用，Y8就能进入被感染的细胞内，关闭病毒的复制。

进一步的研究发现缺失FcRn的小鼠，即使存在病毒特异性IgG，也不能有效的击退流感病毒感染，但是正常的小鼠可以。但是如果是在细胞内对抗病毒感染，那么就不要FcRn这种免疫蛋白。

这项研究将有利于更好的解析抗体如何，以及在哪里对抗病毒，这对于设计新型更有效的疫苗，以及以抗体为基础的治疗具有重要的意义。

除了这项研究以外，朱小平研究组今年早期还接连发表了两篇文章，解析与疾病相关的蛋白（可简化粘膜疫苗制备的融合蛋白，防御性传播疾病的胎盘蛋白）研究最新进展。（生物探索）

相关英文论文摘要：

Intracellular neutralization of viral infection in polarized epithelial cells by neonatal Fc receptor (FcRn)-mediated IgG transport

IgG was traditionally thought to neutralize virions by blocking their attachment to or penetration into mucosal epithelial cells, a common site of exposure to viruses. However, we describe an intracellular neutralizing action for an influenza hemagglutinin-specific monoclonal antibody, Y8-10C2 (Y8), which has neutralizing activity only at an acidic pH. When Y8 was applied to the basolateral surface of Madin–Darby canine kidney cells expressing the rat neonatal Fc receptor for IgG (FcRn), it significantly reduced viral replication following apical exposure of the cell monolayer to influenza virus. Virus neutralization by Y8 mAb was dependent on FcRn expression and its transport of IgG. As both FcRn and Y8 mAb bind their partners only at acidic pH, the Y8 mAb is proposed to carry out its antiviral activity intracellularly. Furthermore, the virus, Y8 mAb, and FcRn colocalized within endosomes, possibly inhibiting the fusion of viral envelopes with endosomal membranes during primary uncoating, and preventing the accumulation of the neutralized viral nucleoprotein antigen in the nucleus. Prophylactic administration of Y8 mAb before viral challenge in WT mice, but not FcRn-KO mice, conferred protection from lethality, prevented weight loss, resulted in a significant reduction in pulmonary virus titers, and largely reduced virus-induced lung pathology. Thus, this study reveals an intracellular mechanism for viral neutralization in polarized epithelial cells that is dependent on FcRn-mediated transport of neutralizing IgG.

英文论文链接: http://www.pnas.org/content/108/45/18406.short