Computational Study of Antibody-Antigen Coevolution Using a Shape-Space Model

B lymphocytes in the adaptive immune system can produce antibody molecules that bind and remove foreign substances (antigen). The binding affinity of antibodies for an antigen can be improved through affinity maturation (AM) – a Darwinian process occurring in the microenvironment called germinal centers (GC). Studying AM process is crucial for understanding how the immune repertoire evolves and for developing efficient vaccine strategies.

In this work, we focus on B cell maturation against HIV infection, where the antigen is also rapidly evolving, creating an evolutionary “arms race”. We develop a shape-space model to describe antibody-antigen coevolution and use stochastic simulations to study how GC compartmentalization and initial antigen diversity affect the course of affinity maturation. We have identified important determinants of maturation outcome and found a critical role played by the degree of conservation of the antigen.