Mixed IgG Fc immune complexes exhibit blended binding profiles and refine FcR affinity estimates

Tan ZC, Lux A, Biburger M, Varghese P, Lees S, Nimmerjahn F, Meyer AS (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 42

Article Number: 112734

Journal Issue: 7

DOI: 10.1016/j.celrep.2023.112734

Abstract

Immunoglobulin G (IgG) antibodies coordinate immune effector responses by interacting with effector cells via fragment crystallizable γ (Fcγ) receptors. The IgG Fc domain directs effector responses through subclass and glycosylation variation. Although each Fc variant has been extensively characterized in isolation, during immune responses, IgG is almost always produced in Fc mixtures. How this influences effector responses has not been examined. Here, we measure Fcγ receptor binding to mixed Fc immune complexes. Binding of these mixtures falls along a continuum between pure cases and quantitatively matches a mechanistic model, except for several low-affinity interactions mostly involving IgG2. We find that the binding model provides refined estimates of their affinities. Finally, we demonstrate that the model predicts effector cell-elicited platelet depletion in humanized mice. Contrary to previous views, IgG2 exhibits appreciable binding through avidity, though it is insufficient to induce effector responses. Overall, this work demonstrates a quantitative framework for modeling mixed IgG Fc-effector cell regulation.

Authors with CRIS profile

Anja Lux Lehrstuhl für Genetik Markus Biburger Lehrstuhl für Genetik Prabha Varghese Lehrstuhl für Genetik Falk Nimmerjahn Lehrstuhl für Genetik

Involved external institutions

University of California Los Angeles (UCLA) US United States (USA) (US)

How to cite

APA:

Tan, Z.C., Lux, A., Biburger, M., Varghese, P., Lees, S., Nimmerjahn, F., & Meyer, A.S. (2023). Mixed IgG Fc immune complexes exhibit blended binding profiles and refine FcR affinity estimates. Cell Reports, 42(7). https://dx.doi.org/10.1016/j.celrep.2023.112734

MLA:

Tan, Zhixin Cyrillus, et al. "Mixed IgG Fc immune complexes exhibit blended binding profiles and refine FcR affinity estimates." Cell Reports 42.7 (2023).

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