Figure 7. Two-component mechanism in tumour cells that leads to activation of Vγ9Vδ2 TCR T cells.
Non-activating phase: no accumulation of phosphoantigens (pAg, yellow stars, which retains GDP-bound RhoB (red circles+GDP) from extranuclear areas. Activating phase component I: Accumulation of phosphoantigens is followed by more GTP-bound RhoB formation (red circles+GTP). GTP-bound RhoB undergoes subcellular re-compartmentalization (black arrows) accumulating at extranuclear areas and facilitates spatial redistribution of BTN3A1 by promoting cytoskeletal trapping (green lines) in the plasma membrane binding to the B30.2 domain proximal connector region (CR) of BTN3A1 (blue hexagon). Activating phase component II: GTP-bound RhoB dissociates (black arrow) from while pAg binds to the B30.2 domain of BTN3A1, which triggers a conformational change of the extracellular region (ER) of BTN3A1 leading to Vγ9Vδ2 TCR T cell activation.