气候变化领域集成服务门户(CCPortal): Influenza hemagglutinin-specific IgA Fc-effector functionality is restricted to stalk epitopes

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DOI	10.1073/pnas.2018102118
	Influenza hemagglutinin-specific IgA Fc-effector functionality is restricted to stalk epitopes
	Freyn A.W.; Han J.; Guthmiller J.J.; Bailey M.J.; Neu K.; Turner H.L.; Rosado V.C.; Chromikova V.; Huang M.; Strohmeier S.; Liu S.T.H.; Simon V.; Krammer F.; Ward A.B.; Palese P.; Wilson P.C.; Nachbagauer R.
发表日期	2021
ISSN	00278424
卷号	118 期号:8
英文摘要	In this study, we utilized a panel of human immunoglobulin (Ig) IgA monoclonal antibodies isolated from the plasmablasts of eight donors after 2014/2015 influenza virus vaccination (Fluarix) to study the binding and functional specificities of this isotype. In this cohort, isolated IgA monoclonal antibodies were primarily elicited against the hemagglutinin protein of the H1N1 component of the vaccine. To compare effector functionalities, an H1-specific subset of antibodies targeting distinct epitopes were expressed as monomeric, dimeric, or secretory IgA, as well as in an IgG1 backbone. When expressed with an IgG Fc domain, all antibodies elicited Fc-effector activity in a primary polymorphonuclear cell-based assay which differs from previous observations that found only stalk-specific antibodies activate the low-affinity FcγRIIIa. However, when expressed with IgA Fc domains, only antibodies targeting the stalk domain showed Fc-effector activity in line with these previous findings. To identify the cause of this discrepancy, we then confirmed that IgG signaling through the high-affinity FcγI receptor was not restricted to stalk epitopes. Since no corresponding high-affinity Fcα receptor exists, the IgA repertoire may therefore be limited to stalk-specific epitopes in the context of Fc receptor signaling. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Fc receptor; IgA; Influenza
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180544
作者单位	Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Department of Integrative Structural and Computational Biology, Scripps Research Institute, San diego, CA 92037, United States; Department of Medicine, Section of Rheumatology, Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, United States; Committee on Immunology, University of Chicago, Chicago, IL 60637, United States; Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, 1190, Austria; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
推荐引用方式 GB/T 7714	Freyn A.W.,Han J.,Guthmiller J.J.,et al. Influenza hemagglutinin-specific IgA Fc-effector functionality is restricted to stalk epitopes[J],2021,118(8).
APA	Freyn A.W..,Han J..,Guthmiller J.J..,Bailey M.J..,Neu K..,...&Nachbagauer R..(2021).Influenza hemagglutinin-specific IgA Fc-effector functionality is restricted to stalk epitopes.Proceedings of the National Academy of Sciences of the United States of America,118(8).
MLA	Freyn A.W.,et al."Influenza hemagglutinin-specific IgA Fc-effector functionality is restricted to stalk epitopes".Proceedings of the National Academy of Sciences of the United States of America 118.8(2021).