Regulation of T cell expansion by antigen presentation dynamics

TL;DR

This paper presents a model explaining how antigen presentation dynamics regulate T cell expansion, influencing immune response size and specificity, and suggests optimal vaccination strategies based on these insights.

Contribution

The study introduces a mathematical model linking antigen decay to T cell proliferation, accounting for affinity and administration kinetics, and optimizing vaccination protocols.

Findings

T cell expansion follows an inverse power law related to initial T cell numbers.

Higher affinity clones suppress lower affinity clones, enhancing response specificity.

Exponentially increasing antigen doses optimize immune response.

Abstract

An essential feature of the adaptive immune system is the proliferation of antigen-specific lymphocytes during an immune reaction to form a large pool of effector cells. This proliferation must be regulated to ensure an effective response to infection while avoiding immunopathology. Recent experiments in mice have demonstrated that the expansion of a specific clone of T cells in response to cognate antigen obeys a striking inverse power law with respect to the initial number of T cells. Here, we show that such a relationship arises naturally from a model in which T cell expansion is limited by decaying levels of presented antigen. The same model also accounts for the observed dependence of T cell expansion on affinity for antigen and on the kinetics of antigen administration. Extending the model to address expansion of multiple T cell clones competing for antigen, we find that higher affinity clones can suppress the proliferation of lower affinity clones, thereby promoting the specificity of the response. Employing the model to derive optimal vaccination protocols, we find that exponentially increasing antigen doses can achieve a nearly optimized response. We thus conclude that the dynamics of presented antigen is a key regulator of both the size and specificity of the adaptive immune response.