T-cell receptor beta constant (TRBC)

The T-cell receptor beta constant (TRBC) region is a vital structural component of the T-cell receptor (TCR) complex, responsible for anchoring the receptor to the cell membrane and facilitating essential signal transduction during antigen recognition [UniProt: P01850]. In humans, the beta chain constant region is encoded by two nearly identical genes, TRBC1 and TRBC2, which are expressed in a mutually exclusive manner on individual T cells due to allelic exclusion [PMID: 29131157]. This biological characteristic provides a unique therapeutic opportunity to treat T-cell malignancies, such as peripheral T-cell lymphoma, by targeting the specific TRBC isoform expressed by the malignant clone [PMID: 35058614]. By selectively eliminating either TRBC1+ or TRBC2+ cells, therapies like CAR-T cells (e.g., AUTO4) can eradicate cancerous T cells while preserving approximately half of the healthy T-cell compartment to maintain cellular immunity [PMID: 34161605]. This approach aims to circumvent the severe, permanent immunodeficiency associated with pan-T-cell targets like CD3 or CD7. Beyond oncology, the TRBC region is central to the adaptive immune system's ability to respond to pathogens and may play a role in the development of autoimmune disorders. Current clinical efforts are primarily focused on developing TRBC1-targeted therapies for patients with relapsed or refractory T-cell lymphomas.

Other names

T-cell receptor beta chain constant regionTRBC1TRBC2TCRBTCRBCT-cell receptor beta constant 1T-cell receptor beta constant 2

Selective depletion of malignant T-cell clones through CAR-T cell-mediated cytotoxicity or antibody-dependent cellular cytotoxicity (ADCC) by targeting the mutually exclusive expression of TRBC1 or TRBC2 isoforms; redirection of T-cell effector functions.