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

T-cell receptor beta constant 2 (TRBC2) is a protein that forms part of the constant region of the T-cell receptor (TCR) beta chain (UniProt P01850). In humans, the TCR beta chain constant region is encoded by two highly homologous genes, TRBC1 and TRBC2, which are expressed in a mutually exclusive manner on the surface of individual T-cells (Maciocia et al., Nature Medicine, 2017). This mutual exclusivity is maintained during malignant transformation, meaning that T-cell lymphomas and leukemias are uniformly either TRBC1-positive or TRBC2-positive. The JX1.1 antibody is a specific binder for the TRBC2 isoform, enabling the development of precision immunotherapies like CAR-T cells (e.g., AUTO5) that target only the TRBC2-expressing population (Autolus Therapeutics, 2023). This strategy allows for the eradication of the malignant clone while sparing the TRBC1-expressing healthy T-cells, which typically constitute approximately 35-40% of the total T-cell repertoire. Consequently, this approach offers a therapeutic window to treat T-cell malignancies without the profound immunosuppression caused by pan-T-cell depletion.

Other names

T-cell receptor beta-2 chain C regionTCRB2TRB@

Selective depletion of TRBC2-expressing T-cells via antibody-mediated or CAR-T cell-mediated cytotoxicity, sparing the TRBC1-expressing T-cell compartment.