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

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.

Early T cell receptor signals globally modulate ligand:receptor affinities during antigen discrimination.

Antigen discrimination by T cells occurs at the junction between a T cell and an antigen-presenting cell. Juxtacrine binding between numerous adhesion, signaling, and costimulatory molecules defines both the topographical and lateral geometry of this cell-cell interface, within which T cell receptor (TCR) and peptide major histocompatibility complex (pMHC) interact. These physical constraints on receptor and ligand movement have significant potential to modulate their molecular binding properties.

Size-based chromatography of signaling clusters in a living cell membrane.

Here we introduce a form of chromatography that can be imposed on the membrane of a living cell. A cell-cell signaling interaction is reconstituted in a hybrid live cell-supported membrane junction. The chromatographic material consists of a hexagonally ordered array of gold nanoparticles (nanodot array), which is fabricated onto the underlying substrate.