Flipping the switch in T cells

Abstract

Immunology\nThe cytoplasmic domains of some CD3 subunits in the T cell receptor complex localize along the inner leaflet of the plasma membrane through electrostatic interactions, which inhibits their activation. Connolly et al. found that the scramblase TMEM16F, which redistributes phosphatidylserine from the inner to the outer leaflet of the plasma membrane, enabled the cytoplasmic domains of CD3 subunits in bystander T cell receptors to disengage from the plasma membrane, leading to enhanced T cell activation. These bystander TCRs were close to antigen-stimulated TCRs and amplified T cell signaling.\n\nSci. Signal. 14 , eabb5146 (2021).