CALY-002 epitope and mode of action. (A) CALY-002 does not prevent IL-15 binding to IL-15Rα. Biotinylated hIL-15 at a single concentration was incubated with immobilized IL-15Rα-Fc in the presence of a titration of antibodies, as described. Data represent mean ± SD of IL-15 binding signal expressed as 450 nM absorbance from one representative experiment. (B) The published structure of the IL-15/IL-15Rαβγ quaternary complex was used to visualize the IL-15 binding epitope of CALY-002. Interleukin-15 is shown in blue, the IL-15 binding motif of CALY-002 in cyan, and IL-15Rβ in orange. The side chain of the critical residues of the binding motif of CALY-002 is highlighted: D109, E112, I116, and N119. K71 of IL-15Rβ directly interacts with D109 of IL-15.