A Monosaccharide Residue Is Sufficient to Maintain Mouse and Human IgG Subclass Activity and Directs IgG Effector Functions to Cellular Fc Receptors
Immunoglobulin G (IgG) glycosylation modulates antibody activity and represents a major source of heterogeneity within antibody preparations. Depending on their glycosylation pattern, individual IgG glycovariants present in recombinant antibody preparations may trigger effects ranging from enhanced...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2015-12-01
|
Series: | Cell Reports |
Subjects: | |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715013273 |
id |
doaj-1946d3ce49244901ad3235a94c8a7d9b |
---|---|
record_format |
Article |
spelling |
doaj-1946d3ce49244901ad3235a94c8a7d9b2020-11-25T01:15:34ZengElsevierCell Reports2211-12472015-12-0113112376238510.1016/j.celrep.2015.11.027A Monosaccharide Residue Is Sufficient to Maintain Mouse and Human IgG Subclass Activity and Directs IgG Effector Functions to Cellular Fc ReceptorsDaniela Kao0Heike Danzer1Mattias Collin2Andrea Groß3Jutta Eichler4Jerko Stambuk5Gordan Lauc6Anja Lux7Falk Nimmerjahn8Chair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, GermanyChair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, GermanyDepartment of Clinical Sciences, Division of Infection Medicine, Biomedical Center B14, Lund University, 221 84 Lund, SwedenDepartment of Chemistry and Pharmacy, University of Erlangen-Nuremberg, Schuhstrasse 19, 91052 Erlangen, GermanyDepartment of Chemistry and Pharmacy, University of Erlangen-Nuremberg, Schuhstrasse 19, 91052 Erlangen, GermanyGenos Glycoscience Research Laboratory, Hondlova 2/11, 10000 Zagreb, CroatiaGenos Glycoscience Research Laboratory, Hondlova 2/11, 10000 Zagreb, CroatiaChair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, GermanyChair of Genetics, Department of Biology, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, 91058 Erlangen, GermanyImmunoglobulin G (IgG) glycosylation modulates antibody activity and represents a major source of heterogeneity within antibody preparations. Depending on their glycosylation pattern, individual IgG glycovariants present in recombinant antibody preparations may trigger effects ranging from enhanced pro-inflammatory activity to increased anti-inflammatory activity. In contrast, reduction of IgG glycosylation beyond the central mannose core is generally believed to result in impaired IgG activity. However, this study reveals that a mono- or disaccharide structure consisting of one N-acetylglucosamine with or without a branching fucose residue is sufficient to retain the activity of the most active human and mouse IgG subclasses in vivo and further directs antibody activity to cellular Fcγ receptors. Notably, the activity of minimally glycosylated antibodies is not predicted by in vitro assays based on a monomeric antibody-Fcγ-receptor interaction analysis, whereas in vitro assay systems using immune complexes are more suitable to predict IgG activity in vivo.http://www.sciencedirect.com/science/article/pii/S2211124715013273cytotoxic antibodiesglycosylationFcγ receptorsIgG |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daniela Kao Heike Danzer Mattias Collin Andrea Groß Jutta Eichler Jerko Stambuk Gordan Lauc Anja Lux Falk Nimmerjahn |
spellingShingle |
Daniela Kao Heike Danzer Mattias Collin Andrea Groß Jutta Eichler Jerko Stambuk Gordan Lauc Anja Lux Falk Nimmerjahn A Monosaccharide Residue Is Sufficient to Maintain Mouse and Human IgG Subclass Activity and Directs IgG Effector Functions to Cellular Fc Receptors Cell Reports cytotoxic antibodies glycosylation Fcγ receptors IgG |
author_facet |
Daniela Kao Heike Danzer Mattias Collin Andrea Groß Jutta Eichler Jerko Stambuk Gordan Lauc Anja Lux Falk Nimmerjahn |
author_sort |
Daniela Kao |
title |
A Monosaccharide Residue Is Sufficient to Maintain Mouse and Human IgG Subclass Activity and Directs IgG Effector Functions to Cellular Fc Receptors |
title_short |
A Monosaccharide Residue Is Sufficient to Maintain Mouse and Human IgG Subclass Activity and Directs IgG Effector Functions to Cellular Fc Receptors |
title_full |
A Monosaccharide Residue Is Sufficient to Maintain Mouse and Human IgG Subclass Activity and Directs IgG Effector Functions to Cellular Fc Receptors |
title_fullStr |
A Monosaccharide Residue Is Sufficient to Maintain Mouse and Human IgG Subclass Activity and Directs IgG Effector Functions to Cellular Fc Receptors |
title_full_unstemmed |
A Monosaccharide Residue Is Sufficient to Maintain Mouse and Human IgG Subclass Activity and Directs IgG Effector Functions to Cellular Fc Receptors |
title_sort |
monosaccharide residue is sufficient to maintain mouse and human igg subclass activity and directs igg effector functions to cellular fc receptors |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2015-12-01 |
description |
Immunoglobulin G (IgG) glycosylation modulates antibody activity and represents a major source of heterogeneity within antibody preparations. Depending on their glycosylation pattern, individual IgG glycovariants present in recombinant antibody preparations may trigger effects ranging from enhanced pro-inflammatory activity to increased anti-inflammatory activity. In contrast, reduction of IgG glycosylation beyond the central mannose core is generally believed to result in impaired IgG activity. However, this study reveals that a mono- or disaccharide structure consisting of one N-acetylglucosamine with or without a branching fucose residue is sufficient to retain the activity of the most active human and mouse IgG subclasses in vivo and further directs antibody activity to cellular Fcγ receptors. Notably, the activity of minimally glycosylated antibodies is not predicted by in vitro assays based on a monomeric antibody-Fcγ-receptor interaction analysis, whereas in vitro assay systems using immune complexes are more suitable to predict IgG activity in vivo. |
topic |
cytotoxic antibodies glycosylation Fcγ receptors IgG |
url |
http://www.sciencedirect.com/science/article/pii/S2211124715013273 |
work_keys_str_mv |
AT danielakao amonosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT heikedanzer amonosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT mattiascollin amonosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT andreagroß amonosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT juttaeichler amonosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT jerkostambuk amonosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT gordanlauc amonosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT anjalux amonosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT falknimmerjahn amonosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT danielakao monosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT heikedanzer monosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT mattiascollin monosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT andreagroß monosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT juttaeichler monosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT jerkostambuk monosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT gordanlauc monosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT anjalux monosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors AT falknimmerjahn monosaccharideresidueissufficienttomaintainmouseandhumaniggsubclassactivityanddirectsiggeffectorfunctionstocellularfcreceptors |
_version_ |
1725152541890576384 |