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. 2023 Jun 19;42(6):112657. doi: 10.1016/j.celrep.2023.112657

Figure 3.

Figure 3

Engineering the IL-21–γc interface modulates downstream signaling pathways

(A) Schematic of the signaling pathways activated by WT IL-21 and the design of IL-21 variants with substitutions along the IL-21–γc interface.

(B) Dose-response curves for phopsho-STAT3 (top) and phospho-STAT1 (bottom) in YT-1 cells stimulated with WT IL-21 or the indicated variants for 20 min and analyzed by flow cytometry. Data are mean ± SD for two replicates, shown as percentage of maximal WT IL-21 MFI.

(C) Normalized Emax values for phopsho-STAT3, calculated from the dose-response curves shown in (B). Data are mean ± SD for two replicates.

(D) Maximum MFI of phospho-STAT3 or phospho-STAT1 in YT-1 cells treated with saturating concentrations of IL-21 or variant. Data are mean ± SD for two replicates. The y axis is scaled to begin at the unstimulated background.

(E) Dose-response curves for phospho-STAT3 in human CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD56+ NK cells. Cells were stimulated with WT IL-21 or the indicated variants for 20 min and analyzed by flow cytometry. Data are mean ± SD for two replicates, shown as percentage of maximal WT IL-21 MFI.

(F) Normalized Emax values for phospho-STAT3 in CD4+, CD8+, CD19+, and CD56+ human PBMCs calculated from dose-response curves shown in (E). Data are mean ± SD for two replicates.