Emergence of clonal selection and affinity maturation in an ab initio microscopic model of immunity

TL;DR

This study introduces a microscopic, sequence-based model of the immune system that demonstrates how clonal selection, affinity maturation, and immunity emerge from molecular interactions and mutation rates.

Contribution

It presents a novel protein-level, microscopic model of immunity that explicitly links population dynamics to molecular properties, showing how immune responses develop.

Findings

Infection outcomes depend on mutation rates of viruses and immunoglobulins.

Potent immunoglobulins emerge through clonal selection and affinity maturation.

Cells develop apoptosis-like behavior to eliminate viruses.

Abstract

Mechanisms of immunity, and of the host-pathogen interactions in general are among the most fundamental problems of medicine, ecology, and evolution studies. Here, we present a microscopic, protein-level, sequence-based model of immune system, with explicitly defined interactions between host and pathogen proteins.. Simulations of this model show that possible outcomes of the infection (extinction of cells, survival with complete elimination of viruses, or chronic infection with continuous coexistence of cells and viruses) crucially depend on mutation rates of the viral and immunoglobulin proteins. Infection is always lethal if the virus mutation rate exceeds a certain threshold. Potent immunoglobulins are discovered in this model via clonal selection and affinity maturation. Surviving cells acquire lasting immunity against subsequent infection by the same virus strain. As a second line of defense cells develop apoptosis-like behavior by reducing their lifetimes to eliminate viruses. These results demonstrate the feasibility of microscopic sequence-based models of immune system, where population dynamics of the evolving B-cells is explicitly tied to the molecular properties of their proteins.