TMEM16F mediates bystander TCR-CD3 membrane dissociation at the immunological synapse and potentiates T cell activation
Audrey Connolly, Rébecca Panès, Margaux Tual, Raphaël Lafortune, Angélique Bellemare‐Pelletier, Étienne Gagnon
Abstract
-dependent activation of the phosphatidylserine scramblase TMEM16F, which was previously implicated in T cell activation, reduced the electrostatic potential of the plasma membrane during immunological synapse formation by locally redistributing phosphatidylserine. This, in turn, increased the dissociation of bystander TCR-CD3 cytoplasmic domains from the plasma membrane and enhanced TCR-dependent signaling and consequently T cell activation. This study establishes the molecular basis for the role of TMEM16F in bystander TCR-induced signal amplification and identifies enhancement of TMEM16F function as a potential therapeutic strategy for promoting T cell activation.