T-cell receptor beta-chain constant domain 2 (TRBC2)

T-cell receptor beta-chain constant domain 2 (TRBC2) is one of two mutually exclusive isoforms of the constant region of the T-cell receptor (TCR) beta chain (UniProt: P01850). During T-cell maturation, genetic rearrangement results in the expression of either TRBC1 or TRBC2 on the cell surface, but never both on a single cell (Maciocia et al., Nature Medicine, 2017). This unique biological property is leveraged in the treatment of T-cell malignancies, which are typically clonal and thus express only one of the two constant regions. By targeting TRBC2 specifically, therapeutic agents like the CAR-T cell therapy AUTO4 can selectively eliminate malignant T-cells while preserving the healthy TRBC1-positive T-cell compartment, thereby maintaining partial immune function (Autolus Therapeutics, 2024). This approach addresses the significant challenge of pan-T-cell aplasia often encountered with other T-cell directed therapies. TRBC2's role is primarily structural within the TCR complex, facilitating signal transduction upon antigen recognition. Its clinical relevance is growing as a biomarker for clonality and a target for precision immunotherapy in hematologic cancers (Horna et al., AJCP, 2021).

Other names

T-cell receptor beta constant 2TRBC2TCR beta chain constant region 2T-cell receptor beta-2 chain C region

Selective depletion of T-cells expressing the TRBC2 constant region via chimeric antigen receptor (CAR) T-cell therapy or monoclonal antibodies.