The adaptive immune system is an extremely complex machinery that continuously evolves to recognize and fight external pathogens. This chase is often made harder by the fact that pathogens also evolve and try to escape.

An important example is HIV, where the virus mutates so quickly that the co-evolutionary process happens in the infected host. I will show that traces of virus-lymphocyte interaction can be seen in longitudinal sequencing data, leading to non-trivial patterns of genetic-changes in the two populations, which can be recapitulated with theoretical models [1].

A second case study is flu. Here the co-evolution happens at the human-population scale, with the virus escaping the immune protection developed in previous infections. I will briefly show that a stochastic model that assumes a low-dimensional antigenic space is able to reproduce several macroscopic properties of the flu evolution [2].

Finally, I will present some ideas of my future research plan. I start by taking a step back and characterize the B-lymphocytes evolution in "healthy" conditions. This baseline can be used as a null dynamics when studying response to strong stimuli (e.g. vaccinations, infections) or co-evolution: deviations can isolate what is specific of the response or constrained by the coevolution.

One important system of application will be the gut microbiome. The immune system co-evolves with the microbes with the purpose of maintaining their diversity, but also protecting the host from the appearance of harmful individuals. Details and quantitative properties of these interactions are largely unknown, and their comprehension can benefit from the application of quantitative methods.

 

[1] Mazzolini, Mora, Walczak. Inspecting the interaction between human immunodeficiency virus and the immune system through genetic turnover. Philos. Trans. R. Soc. B (2023)

[2] Chardès*, Mazzolini*, Mora, Walczak. Evolutionary stability of antigenically escaping viruses. PNAS (2023)