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README.md

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-# [Mixed IgG Fc immune complexes exhibit blended binding profiles and refine FcR affinity estimates](https://www.biorxiv.org/content/10.1101/2023.02.15.528730v1)
+# [Mixed IgG Fc immune complexes exhibit blended binding profiles and refine FcR affinity estimates](https://www.cell.com/cell-reports/fulltext/S2211-1247(23)00745-3)
 
-![Test](https://github.com/meyer-lab/FcRegression.jl/workflows/Test/badge.svg)
-![Build](https://github.com/meyer-lab/FcRegression.jl/workflows/Build/badge.svg)
-
-Immunoglobulin (Ig)G antibodies coordinate immune effector responses by selectively binding to target antigens and then interacting with various effector cells via the Fcγ receptors. The Fc domain of IgG can promote or inhibit distinct effector responses across several different immune cell types through variation based on subclass and Fc domain glycosylation. Extensive characterization of these interactions has revealed how the inclusion of certain Fc subclasses or glycans results in distinct immune responses. During an immune response, however, IgG is produced with mixtures of Fc domain properties, so antigen-IgG immune complexes are likely to almost always be comprised of a combination of Fc forms. Whether and how this mixed composition influences immune effector responses has not been examined. Here, we measured Fcγ receptor binding to immune complexes of mixed Fc domain composition. We found that the binding properties of the mixed-composition immune complexes fell along a continuum between those of the corresponding pure cases. Binding quantitatively matched a mechanistic binding model, except for several low-affinity interactions mostly involving IgG2. We found that the affinities of these interactions are different than previously reported, and that the binding model could be used to provide refined estimates of these affinities. Finally, we demonstrated that the binding model can predict effector-cell elicited platelet depletion in humanized mice, with the model inferring the relevant effector cell populations. Contrary to the previous view in which IgG2 poorly engages with effector populations, we observe appreciable binding through avidity, but insufficient amounts to observe immune effector responses. Overall, this work demonstrates a quantitative framework for reasoning about effector response regulation arising from IgG of mixed Fc composition.
+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.
 
 ## Highlights
 
-- The binding behavior of mixed Fc immune complexes is a blend of the binding properties for each constituent IgG species.
-- An equilibrium, multivalent binding model can be generalized to incorporate immune complexes of mixed Fc composition.
-- Particularly for low-affinity IgG-Fcγ receptor interactions, immune complexes provide better estimates of affinities.
-- The FcγR binding model predicts effector-elicited cell clearance in humanized mice.
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+- Mixed Fc immune complexes bind as a blend of each constituent IgG species
+- A multivalent binding model can be generalized to mixed Fc immune complexes
+- Immune complexes provide better estimates for low IgG-Fcγ receptor affinities
+- The FcγR binding model predicts effector-elicited cell clearance in humanized mice