A physical wiring diagram for the human immune system

Complexity Digest

Jarrod Shilts, Yannik Severin, Francis Galaway, Nicole Müller-Sienerth, Zheng-Shan Chong, Sophie Pritchard, Sarah Teichmann, Roser Vento-Tormo, Berend Snijder & Gavin J. Wright
Nature volume608,pages397–404 (2022)

The human immune system is composed of a distributed network of cells circulating throughout the body, which must dynamically form physical associations and communicate using interactions between their cell-surface proteomes1. Despite their therapeutic potential2, our map of these surface interactions remains incomplete3,4. Here, using a high-throughput surface receptor screening method, we systematically mapped the direct protein interactions across a recombinant library that encompasses most of the surface proteins that are detectable on human leukocytes. We independently validated and determined the biophysical parameters of each novel interaction, resulting in a high-confidence and quantitative view of the receptor wiring that connects human immune cells. By integrating our interactome with expression data, we identified trends in the dynamics of immune interactions and constructed a reductionist mathematical model that…

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