T-cell receptor delta variable 2 (TRDV2) (Vδ2)

The Vδ2 chain of the Vγ9Vδ2 T-cell receptor (TCR) is a defining component of the most abundant gamma-delta (γδ) T-cell subset in human peripheral blood. Unlike conventional alpha-beta T cells, Vγ9Vδ2 T cells recognize non-peptide phosphoantigens, such as isopentenyl pyrophosphate (IPP), in an MHC-independent manner that requires the presence of butyrophilin proteins BTN3A1 and BTN2A1 (Rigau et al., 2020, Science). This unique recognition profile allows these cells to detect metabolic dysregulation in tumor cells and infected cells, making the Vδ2 chain an attractive target for cancer immunotherapy. Therapeutic strategies include bispecific antibodies, known as Gammabodies, which cross-link the Vδ2 chain with tumor-associated antigens to trigger targeted cytotoxicity (LAVA Therapeutics, 2023). Because Vγ9Vδ2 T cells do not recognize MHC-peptide complexes, therapies targeting this receptor carry a lower risk of graft-versus-host disease compared to alpha-beta T-cell-based approaches. Current clinical trials are evaluating Vδ2-targeting agents in both solid tumors and hematological malignancies to leverage the natural anti-tumor properties of these cells (Vyborova et al., 2020, Frontiers in Immunology).

Other names

TRDV2Vdelta2TCR delta chain variable region 2Vd2 chainT-cell receptor delta variable 2

Bispecific T-cell engagement and T-cell receptor agonism