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A BW Reporter System for Studying Receptor-Ligand Interactions
Published on: January 7, 2019
Function-driven design of a surrogate interleukin-2 receptor ligand
Ziwei Tang1,2, Zelin Cheng1,2, Teng Li1,2
1Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, China.
Interleukin (IL) receptors play a pivotal role in immune regulation through coordinated interactions among multiple receptor subunits. Their cognate ligands, interleukins, orchestrate diverse immune responses by engaging distinct subunit combinations. Here, we developed a programmable IL-2 receptor surrogate ligand using a combinatorial bispecific agonist antibody strategy. By employing two complementary cell-based reporter systems that simultaneously monitor IL-2 receptor-mediated STAT5 activation and cell proliferation, we engineered a surrogate IL-2 receptor ligand that exhibits biased activation and differentiation of effector T and NK cells. This modular approach enables the development of tailored cytokine receptor surrogates with customized immunomodulatory functions.
Interleukin (IL) receptors play a pivotal role in immune regulation through coordinated interactions among multiple receptor subunits. Their cognate ligands, interleukins, orchestrate diverse immune responses by engaging distinct subunit combinations. Here, we developed a programmable IL-2 receptor surrogate ligand using a combinatorial bispecific agonist antibody strategy. By employing two complementary cell-based reporter systems that simultaneously monitor IL-2 receptor-mediated STAT5 activation and cell proliferation, we engineered a surrogate IL-2 receptor ligand that exhibits biased activation and differentiation of effector T and NK cells. This modular approach enables the development of tailored cytokine receptor surrogates with customized immunomodulatory functions.

