Revealing Determinants for Antibody-Antigen Coevolutionary Outcome Using a Shape-Space Model

B cells in the adaptive immune system produce antibody molecules that bind foreign antigens for removal. The binding affinity of antibodies for an antigen is improved in vivo through affinity maturation (AM) – a speedy Darwinian process occurring in numerous modest-size B cell populations housed by individual germinal centers (GC). A significant challenge arises when highly mutable pathogens (notably HIV) evolve on similar timescales as do B cell populations, evading an effective immune response.

Existing theoretical studies have ignored demographic fluctuations and precluded alternative evolutionary outcomes. In this talk, I extend the classic shape-space model to describe antibody-antigen coevolution via mutation and mutual selection. Using agent-based stochastic simulations, we show that consideration of population dynamics reveals diverse evolutionary outcomes and uncovers key determinants that can potentially be manipulated, including initial antigen diversity and epitope conservation. Moreover, we find population subdivision may slow down mutational escape of antigen. Finally, we suggest a possible route to evolving cross-reactive antibodies amenable to experimental search.