@article{e2f2359396a54d4eafb2ecf36bcb8ed7,
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.",
keywords = "Clonal expansion, Power law, Precursor frequency, T cells, Vaccination",
author = "Andreas Mayer and Yaojun Zhang and Perelson, {Alan S.} and Wingreen, {Ned S.}",
note = "Funding Information: We thank Gr{\'e}goire Altan-Bonnet for helpful discussions and Gennady Bocharov and Zvi Grossman for providing experimental data. This work was started from discussions at the Kavli Institute of Theoretical Physics, University of California, Santa Barbara and supported in part by NSF Grant PHY-1748958, NIH Grant R25GM067110, and Gordon and Betty Moore Foundation Grant 2919.01. This work was supported by a Lewis–Sigler fellowship (A.M.), the Princeton Center for Theoretical Science (Y.Z.), NSF Grant PHY-1607612 (to Y.Z.), NIH Grants R01-OD011095 (to A.S.P.) and R01-AI028433 (to A.S.P.), and the Center for the Physics of Biological Function funded by NSF Grant PHY-1734030 (to N.S.W. and Y.Z.). Portions of this work were performed under the auspices of US Department of Energy Contract 89233218CNA00000. Funding Information: ACKNOWLEDGMENTS. We thank Gr{\'e}goire Altan-Bonnet for helpful discussions and Gennady Bocharov and Zvi Grossman for providing experimental data. This work was started from discussions at the Kavli Institute of Theoretical Physics, University of California, Santa Barbara and supported in part by NSF Grant PHY-1748958, NIH Grant R25GM067110, and Gordon and Betty Moore Foundation Grant 2919.01. This work was supported by a Lewis– Sigler fellowship (A.M.), the Princeton Center for Theoretical Science (Y.Z.), NSF Grant PHY-1607612 (to Y.Z.), NIH Grants R01-OD011095 (to A.S.P.) and R01-AI028433 (to A.S.P.), and the Center for the Physics of Biological Function funded by NSF Grant PHY-1734030 (to N.S.W. and Y.Z.). Portions of this work were performed under the auspices of US Department of Energy Contract 89233218CNA00000. Publisher Copyright: {\textcopyright} 2019 National Academy of Sciences. All Rights Reserved.",
year = "2019",
doi = "10.1073/pnas.1812800116",
language = "English (US)",
volume = "116",
pages = "5914--5919",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "13",
}