Population Based Selection Shapes the T Cell Receptor Repertoire During Thymic Development

Camaglia, Francesco; Ryvkin, Arie; Greenstein, Erez; Reich-Zeliger, Shlomit; Chain, Benny; Mora, Thierry; Walczak, Aleksandra M.; Friedman, Nir

doi:10.2139/ssrn.4048386

Cited by 1 publication

(1 citation statement)

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“…Selection in the vertebrate immune system happens at many distinct stages within individuals, including T cell receptor selection in the thymus ( Camaglia et al, 2022 and affinity maturation of B cells following an immune challenge Chardès et al, 2022 ; Nourmohammad et al, 2019 ; Nourmohammad et al, 2016 ; Molari et al, 2020 ). Selection also happens at the population level as pathogens and individuals coevolve over time ( Marchi et al, 2019 ; Yan et al, 2019 , for instance, in the evolution of influenza Luksza and Lässig, 2014 ; Yan et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Dynamics of immune memory and learning in bacterial communities

Bonsma-Fisher

Goyal

2023

eLife

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From bacteria to humans, adaptive immune systems provide learned memories of past infections. Despite their vast biological differences, adaptive immunity shares features from microbes to vertebrates such as emergent immune diversity, long-term coexistence of hosts and pathogens, and fitness pressures from evolving pathogens and adapting hosts, yet there is no conceptual model that addresses all of these together. To this end, we propose and solve a simple phenomenological model of CRISPR-based adaptive immunity in microbes. We show that in coexisting phage and bacteria populations, immune diversity in both populations is coupled and emerges spontaneously, that bacteria track phage evolution with a context-dependent lag, and that high levels of diversity are paradoxically linked to low overall CRISPR immunity. We define average immunity, an important summary parameter predicted by our model, and use it to perform synthetic time-shift analyses on available experimental data to reveal different modalities of coevolution. Finally, immune cross-reactivity in our model leads to qualitatively different states of evolutionary dynamics, including an influenza-like traveling wave regime that resembles a similar state in models of vertebrate adaptive immunity. Our results show that CRISPR immunity provides a tractable model, both theoretically and experimentally, to understand general features of adaptive immunity.

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