Abstract
The adaptive humoral immune system of vertebrates functions by evolving a huge repertoire of binding proteins, which target potentially all molecules that come into contact with developing B cells. The key to endowing these binders with immunological activity is the adjustment of antibody structure and affinity against molecular targets. As a result, antibodies with a wide range of affinities and specificities evolve during the lifetime of an individual. A recently developed a quantitative model for the description of antibody homeostasis suggests that a quantitative network can describe the dynamic antibody-antigen interaction space. Here, this molecular interaction space is projected onto an energy landscape defined by entropy and free energy of binding. I introduce the concept of binding fountain energy landscape, which allows the thermodynamic representation of binding events and evolution of binding paths of multiple interactions. I further show that the hypersurface of the binding fountain corresponds to the antibody-antigen interaction network. The binding energy landscape identifies unique properties of B1 cells and natural antibodies, and distinct patterns of thymus independent and thymus dependent antibody responses. Overall, the fountain energy landscape concept of molecular interactions allows a systems biological, thermodynamic perception and description of the functioning of the clonal humoral immune system and generally describes protein evolution in thermodynamic space.
Highlights
The adaptive humoral immune system of vertebrates functions by evolving a huge repertoire of binding proteins, which target potentially all molecules that come into contact with developing B cells
Interpretation of antibody function as a system of regulated binding landscape The binding landscape is the set of all potential interactions in a given fluid with given constituents, each interaction being positioned according to the entropic imbalance, conformation and free energy decrease
The evolution of antibodies shows a similar pattern: promiscuous binding of flexible antibody forms utilized as B-cell receptors scanning the complete conformational space, a selected repertoire of antibodies that change conformation to fit onto the target, and an evolved repertoire of rigid high-affinity binders that perfectly match target conformation
Summary
The adaptive humoral immune system of vertebrates functions by evolving a huge repertoire of binding proteins, which target potentially all molecules that come into contact with developing B cells. Energy landscape and antibody binding Molecular interactions can be described by examining structural, kinetic and thermodynamic properties of the binding. Thermodynamics examines the changes in free energy that accompany a binding event; providing statistical descriptions of enthalpic and entropic components of the interaction.
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