Regulation of T cell expansion by antigen presentation dynamics

Andreas Mayer, Yaojun Zhang, Alan S. Perelson, Ned S. Wingreen

Research output: Contribution to journalArticle

5 Scopus citations

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. Using 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.

Original languageEnglish (US)
Pages (from-to)5914-5919
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number13
DOIs
StatePublished - 2019

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • Clonal expansion
  • Power law
  • Precursor frequency
  • T cells
  • Vaccination

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