FcγR Binding and ADCC Activity of Human IgG Allotypes
Antibody dependent cellular cytotoxicity (ADCC) is an Fc-dependent effector function of IgG important for anti-viral immunity and anti-tumor therapies. NK-cell mediated ADCC is mainly triggered by IgG-subclasses IgG1 and IgG3 through the IgG-Fc-receptor (FcγR) IIIa. Polymorphisms in the immunoglobul...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.00740/full |
| _version_ | 1818906669678067712 |
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| author | Steven W. de Taeye Steven W. de Taeye Arthur E. H. Bentlage Mirjam M. Mebius Joyce I. Meesters Suzanne Lissenberg-Thunnissen David Falck Thomas Sénard Nima Salehi Manfred Wuhrer Janine Schuurman Aran F. Labrijn Theo Rispens Gestur Vidarsson |
| author_facet | Steven W. de Taeye Steven W. de Taeye Arthur E. H. Bentlage Mirjam M. Mebius Joyce I. Meesters Suzanne Lissenberg-Thunnissen David Falck Thomas Sénard Nima Salehi Manfred Wuhrer Janine Schuurman Aran F. Labrijn Theo Rispens Gestur Vidarsson |
| author_sort | Steven W. de Taeye |
| collection | DOAJ |
| description | Antibody dependent cellular cytotoxicity (ADCC) is an Fc-dependent effector function of IgG important for anti-viral immunity and anti-tumor therapies. NK-cell mediated ADCC is mainly triggered by IgG-subclasses IgG1 and IgG3 through the IgG-Fc-receptor (FcγR) IIIa. Polymorphisms in the immunoglobulin gamma heavy chain gene likely form a layer of variation in the strength of the ADCC-response, but this has never been studied in detail. We produced all 27 known IgG allotypes and assessed FcγRIIIa binding and ADCC activity. While all IgG1, IgG2, and IgG4 allotypes behaved similarly within subclass, large allotype-specific variation was found for IgG3. ADCC capacity was affected by residues 291, 292, and 296 in the CH2 domain through altered affinity or avidity for FcγRIIIa. Furthermore, allotypic variation in hinge length affected ADCC, likely through altered proximity at the immunological synapse. Thus, these functional differences between IgG allotypes have important implications for therapeutic applications and susceptibility to infectious-, allo- or auto-immune diseases. |
| first_indexed | 2024-12-19T21:42:54Z |
| format | Article |
| id | doaj.art-7dd572adb41b4228b412bd1779181bed |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T21:42:54Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7dd572adb41b4228b412bd1779181bed2022-12-21T20:04:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-05-011110.3389/fimmu.2020.00740527417FcγR Binding and ADCC Activity of Human IgG AllotypesSteven W. de Taeye0Steven W. de Taeye1Arthur E. H. Bentlage2Mirjam M. Mebius3Joyce I. Meesters4Suzanne Lissenberg-Thunnissen5David Falck6Thomas Sénard7Nima Salehi8Manfred Wuhrer9Janine Schuurman10Aran F. Labrijn11Theo Rispens12Gestur Vidarsson13Sanquin Research and Landsteiner Laboratory, Department of Immunopathology, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Department of Experimental Immunohematology, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Department of Experimental Immunohematology, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsGenmab, Utrecht, NetherlandsGenmab, Utrecht, NetherlandsSanquin Research and Landsteiner Laboratory, Department of Experimental Immunohematology, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, NetherlandsSanquin Research and Landsteiner Laboratory, Department of Immunopathology, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, NetherlandsGenmab, Utrecht, NetherlandsGenmab, Utrecht, NetherlandsSanquin Research and Landsteiner Laboratory, Department of Immunopathology, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsSanquin Research and Landsteiner Laboratory, Department of Experimental Immunohematology, Amsterdam UMC, University of Amsterdam, Amsterdam, NetherlandsAntibody dependent cellular cytotoxicity (ADCC) is an Fc-dependent effector function of IgG important for anti-viral immunity and anti-tumor therapies. NK-cell mediated ADCC is mainly triggered by IgG-subclasses IgG1 and IgG3 through the IgG-Fc-receptor (FcγR) IIIa. Polymorphisms in the immunoglobulin gamma heavy chain gene likely form a layer of variation in the strength of the ADCC-response, but this has never been studied in detail. We produced all 27 known IgG allotypes and assessed FcγRIIIa binding and ADCC activity. While all IgG1, IgG2, and IgG4 allotypes behaved similarly within subclass, large allotype-specific variation was found for IgG3. ADCC capacity was affected by residues 291, 292, and 296 in the CH2 domain through altered affinity or avidity for FcγRIIIa. Furthermore, allotypic variation in hinge length affected ADCC, likely through altered proximity at the immunological synapse. Thus, these functional differences between IgG allotypes have important implications for therapeutic applications and susceptibility to infectious-, allo- or auto-immune diseases.https://www.frontiersin.org/article/10.3389/fimmu.2020.00740/fullantibodiesIgG polymorphismFc gamma receptorantibody dependent cellular cytotoxicityglycosylation |
| spellingShingle | Steven W. de Taeye Steven W. de Taeye Arthur E. H. Bentlage Mirjam M. Mebius Joyce I. Meesters Suzanne Lissenberg-Thunnissen David Falck Thomas Sénard Nima Salehi Manfred Wuhrer Janine Schuurman Aran F. Labrijn Theo Rispens Gestur Vidarsson FcγR Binding and ADCC Activity of Human IgG Allotypes Frontiers in Immunology antibodies IgG polymorphism Fc gamma receptor antibody dependent cellular cytotoxicity glycosylation |
| title | FcγR Binding and ADCC Activity of Human IgG Allotypes |
| title_full | FcγR Binding and ADCC Activity of Human IgG Allotypes |
| title_fullStr | FcγR Binding and ADCC Activity of Human IgG Allotypes |
| title_full_unstemmed | FcγR Binding and ADCC Activity of Human IgG Allotypes |
| title_short | FcγR Binding and ADCC Activity of Human IgG Allotypes |
| title_sort | fcγr binding and adcc activity of human igg allotypes |
| topic | antibodies IgG polymorphism Fc gamma receptor antibody dependent cellular cytotoxicity glycosylation |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.00740/full |
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