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

Abstract

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.

Invasive Streptococcal Infection Can Lead to the Generation of Cross-Strain Opsonic Antibodies

“…To quantify the affinities of the binding IgG against the pathogen, we analyzed the binding curves using a bacterium-antibody binding model ( 25 ) ( Fig. 2E ; also, see Fig.…”

“…Binding curves were analyzed using a GAS antibody binding model based on the transfer matrix method for competitive binding described in reference 25 . The implementation of this model is available on GitHub ( https://doi.org/10.5281/zenodo.4063760 ).…”

MOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity

“…We selected these models based on qualitative characteristics of the curves as well as antibody-antigen binding kinetics (45,46). Death of MOG+ cells as a result of CDC was also best fit by the Gompertz curve with a R 2 of 0.62 (Figure 5B).…”

Gut microbiota and maternal immune transfer at birth influence pre-allergic clinical outcome

“…Opsonization is the process in which the Fab region of antibodies target antigens on pathogens, which can cross-link antigens and allows the free Fc region to promote the elimination of pathogens through various mechanisms, including complement activation and phagocytosis. However, some microbes, most often pathogens, express surface proteins that bind the Fragment crystallizable (Fc) region of antibodies, thereby efficiently reducing the host's ability to eliminate the microbe 71 . Microbes expressing IgG Fc-binding proteins include Streptococci (protein G as well as M and M-like proteins [72][73][74][75] ), Staphylococcus aureus (protein A 76 ).…”