Discussion

Ligand-induced receptor dimerization is an early functional step in receptor activation, representing the most
proximal, functional read-out for Interleukin receptors. It is well understood that the family of Interleukin receptors will
dimerize with the other members of its family leading to a complicated signaling cascade that is critically involved
in a variety of auto-immune, infl ammatory and oncogenic diseases. Here we present a novel application of the
PathHunter® technology to monitor receptor-receptor interactions at the surface of intact live cells, applicable to
diverse receptor types, with a specifi c focus on the interleukin family of receptors. The high specifi city, simplicity of
the assay protocol, large signal to noise ratio, serum tolerance and reproducibility of these assays has enabled their
use in cell-based screening, functional characterization and QC lot release assays. Examples discussed here include
assays for ~80% of all human interleukins, including assays for Ustekinumab and Tocilizumab. These robust assays
have excellent reproducibility, accuracy and precision, demonstrating their suitability for use as QC Lot Release assays.