The CD8α hinge is intrinsically disordered with a dynamic exchange that includes proline cis-trans isomerization.

ABSTRACT: T cells engineered to express artificial chimeric antigen receptors (CARs) that selectively target tumor-specific antigens or deleterious cell types offer transformative therapeutic possibilities. CARs contain an N-terminal extracellular antigen recognition domain, C-terminal intracellular signal transduction domains, and connecting hinge and transmembrane regions, each of which have been varied to optimize targeting and minimize toxicity. We find that a CD22-targeting CAR harboring a CD8α hinge (H) exhibits greater cytotoxicity against a low antigen density CD22⁺ leukemia as compared to an equivalent CAR with a CD28 H. We therefore studied the biophysical and dynamic properties of the CD8α H by nuclear magnetic resonance (NMR) spectroscopy. We find that a large region of the CD

SUBMITTER: Chen X 

PROVIDER: S-EPMC9237829 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature