Human γδ T-cell receptor, extracellular constant region (γδ TCR constant region)

The human γδ T-cell receptor (TCR) is a heterodimeric protein complex found on the surface of γδ T cells, consisting of a gamma (γ) and a delta (δ) chain (Xin et al., 2024). The extracellular constant region of this receptor, encoded by the TRGC and TRDC genes, provides the structural scaffold for the variable domains and is essential for association with the CD3 signaling complex to initiate immune responses (Gully et al., 2024). Unlike the more common αβ TCR, the γδ TCR recognizes antigens in an MHC-independent manner, including phosphoantigens, lipids presented by CD1 molecules, and stress-induced ligands like butyrophilins (Liu et al., 2022). This target is of significant therapeutic interest in oncology, particularly for treating rare and aggressive γδ T-cell malignancies such as hepatosplenic T-cell lymphoma (HSTL) and primary cutaneous γδ T-cell lymphoma (PCGDTL), where CAR-T cells or monoclonal antibodies can be used to specifically deplete the malignant clones (NCI TAB-5073). Additionally, γδ T cells are implicated in the pathogenesis of various autoimmune diseases, such as psoriasis and rheumatoid arthritis, making the constant region a potential target for immunomodulatory therapies (Ferry et al., 2022). Drugs interacting with this target include experimental CAR-T therapies and pan-γδ TCR antibodies designed to either deplete pathogenic T cells or activate them for anti-tumor activity.

Other names

TRGCTRDCT-cell receptor gamma constantT-cell receptor delta constantPan-γδ TCRTCR gamma/delta constant regionTRGC1TRGC2

Targeted depletion of γδ T cells via chimeric antigen receptor (CAR) or antibody-dependent cellular cytotoxicity (ADCC), and modulation of γδ T-cell activation for immunotherapy.