Fig. 1
From: Cancer immunotherapy with γδ T cells: many paths ahead of us
Role of BTN2A1 and BTN3A1 in the activation of human Vγ9Vδ2 γδ T cells. The butyrophilin members BTN2A1 and BTN3A1 are loosely associated on the surface of target cells. a In the homeostatic “resting” state, the intracellular B30.2 signaling domain does not associate with endogenous (tumor-derived IPP) or exogenous (microbe-derived HMBPP) phosphoantigens (pAgs). However, BTN2A1 binds to germ-line-encoded regions of the Vγ9 chain in the homeostatic state. There is also evidence that the CDR3 region of the TCR δ chain interacts with another currently unidentified ligand.37 b In infected cells and tumor cells, exogenous (HMBPP) or endogenous (IPP) pAgs bind to the B30.2 domain and thereby induces a conformational change in the BTN2A1–BTN3A1 complex, resulting in TCR-dependent activation of Vγ9Vδ2 T cells. This step may involve other as yet unidentified CDR3 ligands.36,37 c Agonistic anti-BTN3A antibodies such as clone 20.1 mimic the activity of pAgs by inducing a conformational change in the BTN molecules, leading to γδ T cell activation. The depicted model is based on refs. 35,36,37,38
