@article{200761,
  keywords = {Animals, Mice, Mice, Transgenic, Models, Theoretical, Immunity, Cellular, Antigen Presentation/*physiology, Lymphocyte Activation/immunology/physiology, Models, Immunological, T-Lymphocytes/*physiology, Vaccination/methods, *T cells, *clonal expansion, *power law, *precursor frequency, *vaccination},
  author = {A. Mayer and Y. Zhang and A. S. Perelson and N. S. Wingreen},
  title = {Regulation of T cell expansion by antigen presentation dynamics},
  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. },
  year = {2019},
  journal = {Proc Natl Acad Sci U S A},
  volume = {116},
  edition = {20190308},
  number = {13},
  pages = {5914-5919},
  month = {03/2019},
  isbn = {0027-8424 (Print)0027-8424},
  language = {eng},
}