Felix Meissner
Max Planck Institute of Biochemistry, Munich, Germany

The immune system is unique in its dynamic interplay between diverse cell types. However, a system-wide view of how different immune cells connect, send, and receive biological information has not yet been established. Here, we applied high-resolution mass spectrometry-based proteomics to generate a protein atlas of 28 distinct human immune cell populations in steady and activated states at a depth of more than 10,000 proteins. We show that heterogeneity between cell types arises mainly from expression differences of receptors and ligands thereby linking distinct functional modules of the immune system. By integrating total cellular and secreted proteomes, we deduced paracrine immune dynamics upon microbial challenges and we identified reciprocal communication structures between cellular senders and receivers, underlining the immune system’s ability to unite cellular competencies by coordinated information exchange. Overall, our multi-dimensional data set provides a comprehensive and cell type-resolved proteomic resource of human circulating immune cells, highlighting the functional intercellular connections and complex logic of immune cell interplay.