Optimal evolutionary decision-making to store immune memory

  1. Oskar H Schnaack
  2. Armita Nourmohammad  Is a corresponding author
  1. Max Planck Institute for Dynamics and Self-organization, Germany
  2. University of Washington, United States

Abstract

The adaptive immune system provides a diverse set of molecules that can mount specific responses against a multitude of pathogens. Memory is a key feature of adaptive immunity, which allows organisms to respond more readily upon re-infections. However, differentiation of memory cells is still one of the least understood cell fate decisions. Here, we introduce a mathematical framework to characterize optimal strategies to store memory to maximize the utility of immune response over an organism's lifetime. We show that memory production should be actively regulated to balance between affinity and cross-reactivity of immune receptors for an effective protection against evolving pathogens. Moreover, we predict that specificity of memory should depend on the organism's lifespan, and shorter-lived organisms with fewer pathogenic encounters should store more cross-reactive memory. Our framework provides a baseline to gauge the efficacy of immune memory in light of an organism's coevolutionary history with pathogens.

Data availability

Numerical data generated for all figures and the corresponding code will be provided for publication.

Article and author information

Author details

  1. Oskar H Schnaack

    Statistical Physics of Evolving Systems, Max Planck Institute for Dynamics and Self-organization, Göttingen, Germany
    Competing interests
    No competing interests declared.
  2. Armita Nourmohammad

    Physics, University of Washington, Seattle, United States
    For correspondence
    armita@uw.edu
    Competing interests
    Armita Nourmohammad, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6245-3553

Funding

Deutsche Forschungsgemeinschaft (SFB1310)

  • Armita Nourmohammad

Max Planck Society (MPRG funding)

  • Armita Nourmohammad

University of Washington (Royalty Research Fund: A153352)

  • Armita Nourmohammad

Max Planck Institute for Dynamics and Self-organization (Open-access funding)

  • Armita Nourmohammad

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Arvind Murugan, University of Chicago, United States

Version history

  1. Received: July 22, 2020
  2. Accepted: April 23, 2021
  3. Accepted Manuscript published: April 28, 2021 (version 1)
  4. Version of Record published: May 12, 2021 (version 2)
  5. Version of Record updated: June 10, 2021 (version 3)

Copyright

© 2021, Schnaack & Nourmohammad

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,646
    views
  • 254
    downloads
  • 13
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Oskar H Schnaack
  2. Armita Nourmohammad
(2021)
Optimal evolutionary decision-making to store immune memory
eLife 10:e61346.
https://doi.org/10.7554/eLife.61346

Share this article

https://doi.org/10.7554/eLife.61346

Further reading

    1. Physics of Living Systems
    Maximilian Kurjahn, Antaran Deka ... Stefan Karpitschka
    Research Article

    Filamentous cyanobacteria are one of the oldest and today still most abundant lifeforms on earth, with manifold implications in ecology and economics. Their flexible filaments, often several hundred cells long, exhibit gliding motility in contact with solid surfaces. The underlying force generating mechanism is not yet understood. Here, we demonstrate that propulsion forces and friction coefficients are strongly coupled in the gliding motility of filamentous cyanobacteria. We directly measure their bending moduli using micropipette force sensors, and quantify propulsion and friction forces by analyzing their self-buckling behavior, complemented with analytical theory and simulations. The results indicate that slime extrusion unlikely generates the gliding forces, but support adhesion-based hypotheses, similar to the better-studied single-celled myxobacteria. The critical self-buckling lengths align well with the peaks of natural length distributions, indicating the importance of self-buckling for the organization of their collective in natural and artificial settings.

    1. Cell Biology
    2. Physics of Living Systems
    Ivan Castello-Serrano, Frederick A Heberle ... Ilya Levental
    Research Article

    The organelles of eukaryotic cells maintain distinct protein and lipid compositions required for their specific functions. The mechanisms by which many of these components are sorted to their specific locations remain unknown. While some motifs mediating subcellular protein localization have been identified, many membrane proteins and most membrane lipids lack known sorting determinants. A putative mechanism for sorting of membrane components is based on membrane domains known as lipid rafts, which are laterally segregated nanoscopic assemblies of specific lipids and proteins. To assess the role of such domains in the secretory pathway, we applied a robust tool for synchronized secretory protein traffic (RUSH, Retention Using Selective Hooks) to protein constructs with defined affinity for raft phases. These constructs consist solely of single-pass transmembrane domains (TMDs) and, lacking other sorting determinants, constitute probes for membrane domain-mediated trafficking. We find that while raft affinity can be sufficient for steady-state PM localization, it is not sufficient for rapid exit from the endoplasmic reticulum (ER), which is instead mediated by a short cytosolic peptide motif. In contrast, we find that Golgi exit kinetics are highly dependent on raft affinity, with raft preferring probes exiting the Golgi ~2.5-fold faster than probes with minimal raft affinity. We rationalize these observations with a kinetic model of secretory trafficking, wherein Golgi export can be facilitated by protein association with raft domains. These observations support a role for raft-like membrane domains in the secretory pathway and establish an experimental paradigm for dissecting its underlying machinery.