A physical wiring diagram for the human immune system

Area of Science:

• Immunology
• Systems Biology
• Biophysics

Background:

• The human immune system relies on dynamic cell-cell communication via surface protein interactions.
• A comprehensive map of these immune cell surface interactions is crucial for understanding immune function and developing therapies.
• Current knowledge of immune cell surface interactions remains incomplete.

Purpose of the Study:

• To systematically map direct protein interactions between human leukocyte surface receptors.
• To provide a quantitative and high-confidence view of immune cell connectivity.
• To link these interactions to functional roles in immune responses and intercellular associations.

Main Methods:

• High-throughput surface receptor screening of a recombinant library of human leukocyte surface proteins.
• Independent validation and biophysical parameter determination of novel interactions.
• Integration of interactome data with expression data and development of a mathematical model for cellular connectivity.
• Creation of a multi-tissue single-cell atlas to infer immune interactions.
• Targeted protein stimulation and multiplex high-content microscopy of human leukocytes.

Main Results:

• Systematic mapping of direct protein interactions across most human leukocyte surface proteins.
• Generation of a quantitative, high-confidence interactome of immune cell receptor wiring.
• Identification of trends in immune interaction dynamics and development of a predictive mathematical model.
• Development of an atlas inferring immune interactions across tissues and identifying network hubs.
• Linking specific receptor interactions to functional roles in immune cell communication and responses.

Conclusions:

• This work provides a systematic, systems-level perspective on human immune cell intercellular wiring.
• The quantitative interactome and predictive model offer insights into immune cell connectivity.
• The findings reveal potential functional contexts and therapeutic intervention opportunities for immune receptor interactions.