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Tregs engineered with an orthogonal IL-2 tethered to its receptor persisted without exogenous IL-2 and exhibited superior therapeutic efficacy in a mouse model of type 1 diabetes.
The extent to which JAK/STAT cytokine signaling is functionally redundant or selective remains debated. Here we engineered a “double” orthogonal IL-2/IL-2Rβ/γc ternary system enabling programmable, interference-free activation of each of the 36 mammalian cytokine receptors, and their downstream six STATs, in T cells. A...
This work presents a nondestructive, single-cell approach combining Raman spectroscopy and machine learning that enables rapid cell profiling and therapeutic response prediction and may improve first- and second-line therapy selection assessments for precision medicine.
It is revealed that CD16a transduces piconewton forces and acts as a mechanosensor to facilitate NK activation, and it is demonstrated that CD16a force and the actin foci formation associated with it are essential for the phosphorylation of mechanosensitive adaptor Cas-L and signaling adaptor LAT, reshaping NK cell cyt...
Natural Killer(NK) cells eliminate target cells through antibody-dependent cell-mediated cytotoxicity(ADCC), initiated by CD16a(FcγRIIIa) recognizing the Fc region of antibodies bound to the target cell surface. While the recognition is considered to be driven by CD16a-Fc binding avidity, it fails to explain why Fc mul...
The LINC-seq platform, LINC-seq, recovered known cognate pairs from pooled libraries at up to 95% accuracy and performed simultaneous, library-on-library deep mutational scanning of both partners, and generalizes to any receptor-ligand pair whose trans-engagement drives a reporter.
A role for germline-encoded TCR residues in modulating TCR—MHC recognition and specificity is supported, enabling tolerance of variation at peptide contact sites.
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