Trait-space patterning and the role of feedback in antigen-immunity coevolution

Abstract

Coevolutionary arms races form between interacting populations that constitute each other's environment and respond to mutual changes. This inherently far-from-equilibrium process finds striking manifestations in the adaptive immune system, where highly variable antigens and a finite repertoire of immune receptors coevolve on comparable timescales. This unique challenge to the immune system motivates general questions: How do ecological and evolutionary processes interplay to shape diversity? What determine the endurance and fate of coevolution? Here, we take the perspective of responsive environments and develop a phenotypic model of coevolution between receptors and antigens that both exhibit cross-reactivity (one-to-many responses). The theory predicts that the extent of asymmetry in cross-reactivity is a key determinant of repertoire composition: small asymmetry supports persistent large diversity, whereas strong asymmetry yields long-lived transients of quasispecies in both populations. The latter represents a new type of Turing mechanism. More surprisingly, patterning in the trait space feeds back on population dynamics: spatial resonance between the Turing modes breaks the dynamic balance, leading to antigen extinction or unrestrained growth. Model predictions can be tested via combined genomic and phenotypic measurements. Our work identifies cross-reactivity as an important regulator of diversity and coevolutionary outcome, and reveals the remarkable effect of ecological feedback in pattern-forming systems, which drives evolution toward non-steady states different than the Red Queen persistent cycles.

Molecular tug of war reveals adaptive potential of an immune cell repertoire

“…We demonstrated an unexpected mismatch between the conditions under which training and testing of B cells for antigen recognition are conducted, suggesting that active sensing by cells may not simply optimize receptor potency against current target. In addition, this discrepancy suggests an asymmetry between antigenicity and immunogenicity, i.e., distinction between B-cell activation and antibody recognition, which was predicted to play a large role in determining the course and fate of viral-immune coevolution [55]. To construct alternative cost functions in optimization schemes, a systematic understanding of the physical basis of immune sensing and adaptation is needed to characterize trade-offs between evolvable traits, such as force-stiffness and affinityflexibility relations provided by our model.…”

Active nematic defects in compressible and incompressible flows

“…( 12), as done for instance in Ref. [33]. For the purpose of determining the critical activity, we find it suffices, however, to retain only the wave number k that sets the periodicity of the arch solution and write…”

Coevolutionary transitions emerging from flexible molecular recognition and eco-evolutionary feedback

“…Comparatively fewer studies have considered host-pathogen coevolution ( Kamp and Bornholdt, 2002 ; Luo and Perelson, 2015 ; Cobey et al., 2015 ; Nourmohammad et al., 2016 ); these works often assume constant size of both populations (with recent exceptions ( Bradde et al., 2017 ; Bonsma-Fisher et al., 2018 ; Jiang and Wang, 2019 ; Marchi et al., 2021 )). This assumption is typical in theoretical evolutionary biology and presumably suitable for the chronic stage of infections, and yet it precludes outcomes other than viral persistence, and neglects potential feedback between ecological dynamics and evolution in a host .…”