Marsland, Robert;
Howell, Owen;
Mayer, Andreas;
Mehta, Pankaj;
(2021)
Tregs self-organize into a computing ecosystem and implement a sophisticated optimization algorithm for mediating immune response.
Proceedings of the National Academy of Sciences of USA
, 118
(1)
, Article e2011709118. 10.1073/pnas.2011709118.
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Abstract
Regulatory T cells (Tregs) play a crucial role in mediating immune response. Yet an algorithmic understanding of the role of Tregs in adaptive immunity remains lacking. Here, we present a biophysically realistic model of Treg-mediated self-tolerance in which Tregs bind to self-antigens and locally inhibit the proliferation of nearby activated T cells. By exploiting a duality between ecological dynamics and constrained optimization, we show that Tregs tile the potential antigen space while simultaneously minimizing the overlap between Treg activation profiles. We find that for sufficiently high Treg diversity, Treg-mediated self-tolerance is robust to fluctuations in self-antigen concentrations but lowering the Treg diversity results in a sharp transition-related to the Gardner transition in perceptrons-to a regime where changes in self-antigen concentrations can result in an autoimmune response. We propose an experimental test of this transition in immune-deficient mice and discuss potential implications for autoimmune diseases.
| Type: | Article |
|---|---|
| Title: | Tregs self-organize into a computing ecosystem and implement a sophisticated optimization algorithm for mediating immune response |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1073/pnas.2011709118 |
| Publisher version: | https://doi.org/10.1073/pnas.2011709118 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, adaptive immunity, Tregs, optimization, ecology, biophysics, REGULATORY T-CELLS, AUTOIMMUNE-DISEASES, TOLERANCE, DIVERSITY, POPULATION, REPERTOIRE, SELECTION, BIOLOGY, MICE |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10146939 |
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