Role of CD277/butyrophilin-3A in triggering human γδ T-cell activation. (A) The ubiquitously expressed CD277 molecule is not recognized by the Vγ9Vδ2 T-cell receptor (left). Upon incubation with agonistic anti-CD277 mAbs, changes (mobility and/or conformation) are induced in the CD277 molecule such that Vγ9Vδ2 T cells are activated in a T-cell receptor–dependent manner (right). (B) Some tumor cells are poorly recognized by Vγ9Vδ2 T cells (left). Upon treatment with aminobisphosphonates (n-BP), increased levels of phosphoantigens are produced that induce changes in the membrane mobility of CD277 molecules leading to activation of Vγ9Vδ2 T cells (right). Professional illustration by Alice Y. Chen.