Influenza hemagglutinin-specific IgA Fc-effector functionality is restricted to stalk epitopes.

Autor:	Freyn AW; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Han J; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037., Guthmiller JJ; Department of Medicine, Section of Rheumatology, Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637., Bailey MJ; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Neu K; Department of Medicine, Section of Rheumatology, Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637., Turner HL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037., Rosado VC; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Chromikova V; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Huang M; Department of Medicine, Section of Rheumatology, Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637.; Committee on Immunology, The University of Chicago, Chicago, IL 60637., Strohmeier S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029.; Department of Biotechnology, University of Natural Resources and Life Sciences, 1190 Vienna, Austria., Liu STH; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Simon V; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Krammer F; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Ward AB; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037., Palese P; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; peter.palese@mssm.edu raffael.nachbagauer@gmail.com.; Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029., Wilson PC; Department of Medicine, Section of Rheumatology, Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637.; Committee on Immunology, The University of Chicago, Chicago, IL 60637., Nachbagauer R; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029; peter.palese@mssm.edu raffael.nachbagauer@gmail.com.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Feb 23; Vol. 118 (8).
DOI:	10.1073/pnas.2018102118
Abstrakt:	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. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
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