Differential recognition of AML cells by Vδ1 (DOT) and Vδ2 γδ T cells. (Left) Vδ1/DOT cells express a Vδ1-encoded T-cell receptor (TCR) and the activating NK receptors NKG2D, DNAM-1, and NKp30. Although the TCR plays no major role, the study by Mensurado et al shows that the activation of DOT cells is primarily due to the interaction of DNAM-1 with its ligand PVR/CD155, and the DNAM-1 ligand nectin-2 is not relevant. The NKp30/B7-H6 interaction is also important. AML cells usually lack the expression of ligands for the activating NKG2D receptor. (Right) Vδ2 T cells recognize transformed cells including AML by sensing endogenous phosphoantigens (pAg) via the TCR in a BTN (BTN3A1/BTN2A1)-dependent manner. Vδ2 T cells also express NKG2D, which contributes to Vδ2 T-cell activation in case of NKG2D ligand-expressing target cells (usually solid cancers).^2-4 Professional illustration by Patrick Lane, ScEYEnce Studios.