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Regulation of T cell expansion by antigen presentation dynamics.

Author(s): Mayer, Andreas; Zhang, Yaojun; Perelson, Alan; Wingreen, Ned

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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.
Publication Date: 8-Mar-2019
Electronic Publication Date: 8-Mar-2019
Citation: Mayer, Andreas, Zhang, Yaojun, Perelson, Alan S, Wingreen, Ned S. (2019). Regulation of T cell expansion by antigen presentation dynamics.. Proceedings of the National Academy of Sciences of the United States of America, 116 (13), 5914 - 5919. doi:10.1073/pnas.1812800116
DOI: doi:10.1073/pnas.1812800116
ISSN: 0027-8424
EISSN: 1091-6490
Pages: 5914 - 5919
Language: eng
Type of Material: Journal Article
Journal/Proceeding Title: Proceedings of the National Academy of Sciences of the United States of America
Version: Final published version. This is an open access article.

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