Butyrophilin subfamily 2 member A1 (BTN2A1) (BTN2A1)

Butyrophilin subfamily 2 member A1 (BTN2A1) is a type I transmembrane glycoprotein that belongs to the butyrophilin family and the immunoglobulin superfamily. It is a critical mediator of the human immune response, specifically serving as an essential ligand for the activation of Vγ9Vδ2 T cells, the predominant γδ T-cell subset in human peripheral blood (Rigau et al., 2020, Nature). BTN2A1 functions by directly binding to the Vγ9 chain of the T-cell receptor (TCR) in a process that requires the presence of intracellular phosphoantigens (pAg) and the cooperation of the related protein BTN3A1 (Karunakaran et al., 2020, Science). In many cancer types, the mevalonate pathway is dysregulated, leading to the accumulation of pAgs which signals through the BTN2A1/BTN3A1 complex to alert γδ T cells to the presence of malignant cells. Therapeutic strategies, such as the monoclonal antibody ICT01, target BTN2A1 on tumor cells to act as an agonist, mimicking the pAg-induced activation signal to recruit and activate Vγ9Vδ2 T cells for tumor cell lysis (Imcheck Therapeutics, 2024). This target is currently being investigated in clinical trials for both solid tumors and hematological malignancies due to its ability to harness the potent anti-tumor activity of γδ T cells.

Other names

Butyrophilin 2A1BT2.1BK14Butyrophilin-like protein 2A1

Agonistic monoclonal antibodies bind to the extracellular domain of BTN2A1 on tumor cells, inducing a conformational change or stabilizing its association with BTN3A1 and the Vγ9Vδ2 T-cell receptor (TCR), which triggers γδ T-cell-mediated cytotoxicity against the target cell.