GSE64713 | Datasets2Tools

General Information

Accession	GSE64713
Title	Regulating Interleukin-2 activity with engineered receptor signaling clamps
Description	Interleukin-2 (IL-2) is a pleiotropic cytokine that regulates lymphocyte function by signaling through heterodimerization of the IL-2R and c receptor subunits. Previously, we engineered an IL-2 superkine (H9) with enhanced affinity for IL-2R. Here, we describe next-generation IL-2 variants that function as receptor signaling clamps. They retain high-affinity for IL-2R, thereby inhibiting binding of endogenous IL-2, but their engagement of c is weakened, thereby attenuating IL-2R-c heterodimerization. These IL-2 analogues act as partial agonists and can differentially affect lymphocytes poised at distinct activation thresholds. Moreover, one of these variants potently antagonized IL-2 and IL-15 signaling and function better than blocking antibodies against IL-2R or IL-2R. Furthermore, this mutein prolonged survival in a model of graft versus host disease and blocked spontaneous proliferation of smoldering adult T-cell leukemia (ATL) T cells ex vivo. This receptor-clamping approach may be a general mechanism-based strategy for engineering cytokine partial agonists for therapeutic immunomodulation.
Landing Page	https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE64713
Repository	Gene Expression Omnibus