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The Role of Antigen-Competitive Dynamics in Regulating the Immune Response

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Abstract

The clonal expansion of T cells during an infection is tightly regulated to ensure an appropriate immune response against invading pathogens. Although experiments have mapped the trajectory from expansion to contraction, the interplay between mechanisms that control this response is not fully understood. Based on experimental data, we propose a model in which the dynamics of CD4+ T cell expansion is controlled through the interactions between T cells and antigen-presenting cells, where T cell stimulation is proportional to antigen availability, and antigen availability is regulated through downregulation of antigen by T cells. This antigen-dependent-feedback mechanism operates alongside an intrinsic reduction in cell proliferation rate that may also be responsible for slowing expansion. Our model can successfully predict T cell recruitment rates into division, expansion, and clonal burst size per cell when initial precursors are varied or when T cells are introduced late into an ongoing immune response. Importantly, the findings demonstrate that a feedback mechanism between T cells and antigen-presenting cells, along with a reduction in cell proliferation rate, can explain the ability of the immune system to adapt its response to variations in initial conditions or changes that occur later in the response, ensuring a robust yet controlled line of defence against pathogens.

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Acknowledgements

The authors gratefully acknowledge support for this work through Australian Government Research Training Program Scholarship (PP), the Australian Research Council Discovery Project DP180101512 (PSK).

Funding

This study was funded by Australian Government Research Training Program Scholarship (PP), the Australian Research Council Discovery Project DP180101512 (PSK).

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Author notes

  1. Peter S. Kim and Barbara Fazekas de St Groth: These authors contributed equally.

Authors and Affiliations

  1. School of Mathematics and Statistics, The University of Sydney, Sydney, NSW, 2006, Australia

    Pantea Pooladvand & Peter S. Kim

  2. Discipline of Pathology, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia

    Barbara Fazekas de St Groth

Authors
  1. Pantea Pooladvand
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  2. Peter S. Kim
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  3. Barbara Fazekas de St Groth
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Correspondence to Pantea Pooladvand.

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Pooladvand, P., Kim, P.S. & Fazekas de St Groth, B. The Role of Antigen-Competitive Dynamics in Regulating the Immune Response. Bull Math Biol 83, 40 (2021). https://doi.org/10.1007/s11538-021-00867-7

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  • DOI: https://doi.org/10.1007/s11538-021-00867-7

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