Dissecting FcγR Regulation through a Multivalent Binding Model

Robinett RA, Guan N, Lux A, Biburger M, Nimmerjahn F, Meyer AS (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Cell Systems Elsevier

Book Volume: 7

Pages Range: 41-48.e5

Journal Issue: 1

DOI: 10.1016/j.cels.2018.05.018

Abstract

Many immune receptors transduce activation across the plasma membrane through their clustering. With Fcγ receptors (FcγRs), this clustering is driven by binding to antibodies of differing affinities that are in turn bound to multivalent antigen. As a consequence of this activation mechanism, accounting for and rationally manipulating immunoglobulin (Ig)G effector function is complicated by, among other factors, differing affinities between FcγR species and changes in the valency of antigen binding. In this study, we show that a model of multivalent receptor-ligand binding can effectively account for the contribution of IgG-FcγR affinity and immune complex valency. This model in turn enables us to make specific predictions about the effect of immune complexes of defined composition. In total, these results enable both rational immune complex design for a desired IgG effector function and the deconvolution of effector function by immune complexes. Robinett et al. show that a multivalent binding model can predict antibody binding to immune effector cells. By using this model with measurements of the FcγR combinations expressed across effector populations, they are able to predict the outcome of tumor-targeted antibodies and identify the essential innate cell types. These results inform the further rational design of therapeutic antibodies and potentially antibody combinations.

Authors with CRIS profile

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

Involved external institutions

Massachusetts Institute of Technology (MIT) US United States (USA) (US) University of California Los Angeles (UCLA) US United States (USA) (US)

How to cite

APA:

Robinett, R.A., Guan, N., Lux, A., Biburger, M., Nimmerjahn, F., & Meyer, A.S. (2018). Dissecting FcγR Regulation through a Multivalent Binding Model. Cell Systems, 7(1), 41-48.e5. https://doi.org/10.1016/j.cels.2018.05.018

MLA:

Robinett, Ryan A., et al. "Dissecting FcγR Regulation through a Multivalent Binding Model." Cell Systems 7.1 (2018): 41-48.e5.

BibTeX: Download