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HA抗体介导的FcγRIIIa活性既依赖于FcR结合，也依赖于HA与唾液酸之间的相互作用。

HA Antibody-Mediated FcγRIIIa Activity Is Both Dependent on FcR Engagement and Interactions between HA and Sialic Acids.

作者信息

Cox Freek, Kwaks Ted, Brandenburg Boerries, Koldijk Martin H, Klaren Vincent, Smal Bastiaan, Korse Hans J W M, Geelen Eric, Tettero Lisanne, Zuijdgeest David, Stoop Esther J M, Saeland Eirikur, Vogels Ronald, Friesen Robert H E, Koudstaal Wouter, Goudsmit Jaap

机构信息

Janssen Prevention Center, Janssen Pharmaceutical Companies of Johnson & Johnson , Leiden , Netherlands.

出版信息

Front Immunol. 2016 Sep 29;7:399. doi: 10.3389/fimmu.2016.00399. eCollection 2016.

DOI:10.3389/fimmu.2016.00399
PMID:27746785
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5040702/
Abstract

Interactions with receptors for the Fc region of IgG (FcγRs) have been shown to contribute to the protection against influenza A viruses provided by broadly neutralizing antibodies (bnAbs) that bind to the viral hemagglutinin (HA) stem. In particular, Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) has been shown to contribute to protection by stem-binding bnAbs. Fc-mediated effector functions appear not to contribute to protection provided by strain-specific HA head-binding antibodies. We used a panel of anti-stem and anti-head influenza A and B monoclonal antibodies with identical human IgG1 Fc domains and investigated their ability to mediate ADCC-associated FcγRIIIa activation. Antibodies which do not interfere with sialic acid binding of HA can mediate FcγRIIIa activation. However, the FcγRIIIa activation was inhibited when a mutant HA, unable to bind sialic acids, was used. Antibodies which block sialic acid receptor interactions of HA interfered with FcγRIIIa activation. The inhibition of FcγRIIIa activation by HA head-binding and sialic acid receptor-blocking antibodies was confirmed in plasma samples of H5N1 vaccinated human subjects. Together, these results suggest that in addition to Fc-FcγR binding, interactions between HA and sialic acids on immune cells are required for optimal Fc-mediated effector functions by anti-HA antibodies.

摘要

与IgG的Fc区域受体（FcγRs）的相互作用已被证明有助于由结合病毒血凝素（HA）茎部的广泛中和抗体（bnAbs）提供的针对甲型流感病毒的保护。特别是，Fc介导的抗体依赖性细胞毒性（ADCC）已被证明有助于茎部结合bnAbs提供的保护。Fc介导的效应功能似乎对菌株特异性HA头部结合抗体提供的保护没有贡献。我们使用了一组具有相同人IgG1 Fc结构域的抗甲型和乙型流感病毒茎部和头部的单克隆抗体，并研究了它们介导ADCC相关FcγRIIIa激活的能力。不干扰HA与唾液酸结合的抗体可以介导FcγRIIIa激活。然而，当使用不能结合唾液酸的突变型HA时，FcγRIIIa激活受到抑制。阻断HA与唾液酸受体相互作用的抗体干扰了FcγRIIIa激活。在接种H5N1疫苗的人类受试者的血浆样本中证实了HA头部结合和唾液酸受体阻断抗体对FcγRIIIa激活的抑制作用。总之，这些结果表明，除了Fc-FcγR结合外，免疫细胞上的HA与唾液酸之间的相互作用对于抗HA抗体实现最佳Fc介导的效应功能是必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d942/5040702/0e685ba9d67e/fimmu-07-00399-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d942/5040702/64e92d585b9c/fimmu-07-00399-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d942/5040702/89268ba217c8/fimmu-07-00399-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d942/5040702/e58e7324c6c6/fimmu-07-00399-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d942/5040702/0e685ba9d67e/fimmu-07-00399-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d942/5040702/64e92d585b9c/fimmu-07-00399-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d942/5040702/89268ba217c8/fimmu-07-00399-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d942/5040702/e58e7324c6c6/fimmu-07-00399-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d942/5040702/0e685ba9d67e/fimmu-07-00399-g004.jpg

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