fimmu-11-00740 May 4, 2020 Time: 17:25 # 1 ORIGINAL RESEARCH published: 06 May 2020 doi: 10.3389/fimmu.2020.00740 FcgR Binding and ADCC Activity of Human IgG Allotypes Steven W. de Taeye1,2*†, Arthur E. H. Bentlage2, Mirjam M. Mebius3, Joyce I. Meesters3, Suzanne Lissenberg-Thunnissen2, David Falck4, Thomas Sénard4, Nima Salehi1, Manfred Wuhrer4, Janine Schuurman3, Aran F. Labrijn3, Theo Rispens1‡ and Gestur Vidarsson2‡ 1 Sanquin Research and Landsteiner Laboratory, Department of Immunopathology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands, 2 Sanquin Research and Landsteiner Laboratory, Department of Experimental Edited by: Immunohematology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands, 3 Genmab, Utrecht, Eric O. Long, Netherlands, 4 Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, Netherlands National Institute of Allergy and Infectious Diseases (NIAID), United States Antibody dependent cellular cytotoxicity (ADCC) is an Fc-dependent effector function Reviewed by: of IgG important for anti-viral immunity and anti-tumor therapies. NK-cell mediated Amy W. Chung, ADCC is mainly triggered by IgG-subclasses IgG1 and IgG3 through the IgG-Fc- The University of Melbourne, Australia receptor (FcgR) IIIa. Polymorphisms in the immunoglobulin gamma heavy chain gene Geoffrey Thomas Hart, University of Minnesota Twin Cities, likely form a layer of variation in the strength of the ADCC-response, but this has United States never been studied in detail. We produced all 27 known IgG allotypes and assessed *Correspondence: FcgRIIIa binding and ADCC activity. While all IgG1, IgG2, and IgG4 allotypes behaved Steven W. de Taeye
[email protected]; similarly within subclass, large allotype-specific variation was found for IgG3.