Membrane Association Transforms an Inert Anti-TCRβ Fab' Ligand into a Potent T Cell Receptor Agonist.

ABSTRACT: The natural peptide-major histocompatibility complex (pMHC) ligand for T cell receptors (TCRs) is inactive from solution yet capable of activating T cells at single-molecule levels when membrane-associated. This distinctive feature stems from the mechanism of TCR activation, which is thought to involve steric phosphatase exclusion as well as direct mechanical forces. It is possible to defeat this mechanism and activate T cells with solution ligands by cross-linking pMHC or using multivalent antibodies to TCR. However, these widely used strategies activate TCRs through a nonphysiological mechanism and can produce different activation profiles than natural, monovalent, membrane-associated pMHC. Here, we introduce a strictly monovalent anti-TCRβ H57 Fab' ligand that, when coupled to a support

SUBMITTER: Lin JJ 

PROVIDER: S-EPMC7300389 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature