Mature TGF-β isoforms, which are covalent dimers, signal by binding to three types of cell surface receptors, the type I, II and III TGF-β receptors. A complex composed of the TGF-β ligand and the type I and II receptors is required for signaling. The type II receptor is responsible for recruiting TGF-β into the heteromeric ligand/type I receptor/type II receptor complex. The purpose of this study was to test for the extent that avidity contributes to receptor affinity. Using a surface plasmon resonance (SPR)-based biosensor (the BIACORE), we captured the extracellular domain of the type II receptor (TβRIIED) at the biosensor surface in an oriented and stable manner by using a de novo designed coiled-coil (E/K coil) heterodimerizing system. We characterized the kinetics of binding of three TGF-β isoforms to this immobilized TβRIIED. The results demonstrate that the stoichiometry of TGF-β binding to TβRIIED was one dimeric ligand to two receptors. All three TGF-β isoforms had rapid and similar association rates, but different dissociation rates, which resulted in the equilibrium dissociation constants being approximately 5pM for the TGF-β1 and -β3 isoforms, and 5nM for the TGF-β2 isoform. Since these apparent affinities are at least four orders of magnitude higher than those determined when TGF-β was immobilized, and are close to those determined for TβRII at the cell surface, we suggest that avidity contributes significantly to high affinity receptor binding both at the biosensor and cell surfaces. Finally, we demonstrated that the coiled-coil immobilization approach does not require the purification of the captured protein, making it an attractive tool for the rapid study of any protein–protein interaction.