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

DOI10.1073/PNAS.2011709118MaRDI QIDQ5073252zbMATH OpenOpenAlexWikidataFDO

Authors Owen Howell, Pankaj Mehta

Publication date 5 May 2022

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

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

Mathematics Subject Classification ID

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

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.

Recommendations

• Optimal T cell cross-reactivity and the role of regulatory T cells
• Immunological self-tolerance: Lessons from mathematical modeling
• Self-tolerance and autoimmunity in a regulatory T cell model
• Regulatory T cell adjustment of quorum growth thresholds and the control of local immune responses
• Emergent group dynamics governed by regulatory cells produce a robust primary T cell response

Cites work

• Machine learning as ecology
• Mathematical and Computational Challenges in Population Biology and Ecosystems Science
• Pattern recognition and machine learning.
• Quantitative immunology for physicists
• Statistical Physics of Spin Glasses and Information Processing
• The space of interactions in neural network models

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

This page was built for publication: Tregs self-organize into a computing ecosystem and implement a sophisticated optimization algorithm for mediating immune response

Report a bug (only for logged in users!)Click here to report a bug for this page (MaRDI item Q5073252)