Tregs self-organize into a computing ecosystem and implement a sophisticated optimization algorithm for mediating immune response

DOI10.1073/PNAS.2011709118zbMATH Open1485.92029arXiv2012.00252OpenAlexW3117127514WikidataQ104609818 ScholiaQ104609818MaRDI QIDQ5073252FDOQ5073252

Authors: Owen Howell, Pankaj Mehta 

Publication date: 5 May 2022

Published in: Proceedings of the National Academy of Sciences (Search for Journal in Brave)

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 auto-immune response. We propose a novel experimental test of this transition in immune-deficient mice and discuss potential implications for autoimmune diseases.

Full work available at URL: https://arxiv.org/abs/2012.00252

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Mathematics Subject Classification ID

Applications of mathematical programming (90C90) Physiology (general) (92C30)

Cites Work

• Pattern recognition and machine learning.
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• Statistical Physics of Spin Glasses and Information Processing
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Cited In (2)

• Emergent group dynamics governed by regulatory cells produce a robust primary T cell response
• T-cell receptor optimization with reinforcement learning and mutation polices for precision immunotherapy

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