Fig. 1: TGF-β→IL-2 cytokine adaptors compel IL-2 receptor signaling in the presence of TGF-β.
a Conceptual overview of an adaptor. b Schematic illustrating cytokine adaptors, which convert an inhibitory cytokine into a stimulatory cytokine by blocking the inhibitory cytokine from binding to its receptor and instead compelling dimerization of the stimulatory receptor. Model is based on IL-2R (PDB ID: 2B5I) and TGF-βR (PDB ID: 2PJY). c Model comparing natural TGF-β signaling through TGF-βRI and TGF-βRII (left) vs. signaling through TGF-β→IL-2 cytokine adaptors (right) which dimerize IL-2Rβ and gamma-c (γc). Adaptor molecules are comprised of scFv GC1008 linked to a VHH against IL-2Rβ (IL-2RβNb6) or a VHH against γc (γcNb6). d Cartoon representations of TGF-β Adaptor T.1 and Adaptor T.2. e, f Adaptors T.1 and T.2 signal through pSTAT5 in the presence of TGF-β. e Dose–response curves for phospho-STAT5 in YT-1 cells stimulated for 20 min with human IL-2 or TGF-β with equimolar Adaptor T.1 and Adaptor T.2. Data plotted as the mean of n = 2 technical replicates. Data are representative of N = 3 independent experiments (n = 2, N = 3). f Phospho-STAT5 Emax calculated from dose–response curves in YT-1 cells normalized to IL-2 Emax. Bar graphs represent mean, n = 2, N = 3. Source data are provided as a Source data file.
