Cell-cell interactions mediated by cell surface receptor-ligand pairs in the immune system are often of low affinity and transient in nature. To begin to study these weak interactions, it is desirable to devise a generally applicable method for screening for and enriching cells expressing low-affinity ligands for specific cell surface receptors. We describe here an experimental strategy that uses a multivalent form of protein as a probe to identify and characterize cognate ligand(s) of myeloid

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... ell surface receptors. Recombinant fusion proteins containing the receptor protein fragment of interest fused to a truncated mouse Fc domain and a unique biotinylation signal are produced, biotinylated, and coupled to (strept) avidin-coated fluorescent or paramagnetic microspheres. These multivalent microparticle probes are then used to screen or capture cells expressing the cognate cellular ligand(s).