A Predictive Model of Antibody Binding in the Presence of IgG-Interacting Bacterial Surface Proteins

Many bacteria can interfere with how antibodies bind to their surfaces. This bacterial antibody targeting makes it challenging to predict the immunological function of bacteria-associated antibodies. The M and M-like proteins of group A streptococci (GAS) exhibit IgGFc-binding regions, which they use to reverse IgG binding orientation depending on the host environment. Unraveling the mechanism behind these binding characteristics may identify conditions under which bound IgG can drive an efficient immune response. Here, we have developed a biophysical model for describing these complex protein-antibody interactions. We show how the model can be used as a tool for studying the binding behavior of various IgG samples to M protein by performing in silico simulations and correlating this data with experimental measurements. Besides its use for mechanistic understanding, this model could potentially be used as a tool to aid in the development of antibody treatments. We illustrate this by simulating how IgG binding to GAS in serum is altered as specified amounts of monoclonal or pooled IgG is added. Phagocytosis experiments link this altered antibody binding to a physiological function and demonstrate that it is possible to predict the effect of an IgG treatment with our model. Our study gives a mechanistic understanding of bacterial antibody targeting and provides a tool for predicting the effect of antibody treatments in the presence of bacteria with IgG-modulating surface proteins.

Automated summary

Bacteria can interfere with antibody binding to their surfaces, posing a challenge in predicting the immunological function of bacteria-associated antibodies. The M and M-like proteins of group A streptococci have been found to reverse IgG binding orientation based on the host environment. A biophysical model has been developed to study these protein-antibody interactions and could potentially aid in the development of antibody treatments. Simulations have shown that altering IgG binding to GAS in serum can have physiological effects, providing a tool for predicting the impact of antibody treatments in the presence of bacteria with IgG-modulating surface proteins.