T-cell receptor alpha-beta heterodimer (TCR alpha-beta) (TCR alpha-beta)

The T-cell receptor (TCR) alpha-beta heterodimer is the primary antigen-recognition molecule on the surface of approximately 95% of mature peripheral blood T cells [1, 4]. It consists of two highly variable polypeptide chains, alpha and beta, which form a complex with invariant CD3 subunits to mediate signal transduction [1, 16]. The TCR specifically recognizes processed peptide antigens presented by Major Histocompatibility Complex (MHC) molecules, a process fundamental to the adaptive immune response against pathogens and tumors [1, 4]. This interaction allows T cells to distinguish between self and non-self, enabling the targeted elimination of infected or malignant cells [4, 7]. In oncology, the TCR is a central target for therapies such as TCR-engineered T cells (TCR-T) and bispecific TCR engagers like tebentafusp, which redirect the immune system to attack specific cancer antigens [2, 5]. These therapies are particularly valuable for targeting intracellular proteins that are not accessible to standard antibody-based treatments [2, 5]. Conversely, the TCR is targeted for inhibition or depletion in the context of autoimmune diseases and graft-versus-host disease to prevent unwanted immune attacks [8, 11]. Safety considerations for TCR-targeting agents include the risk of cytokine release syndrome and potential off-target reactivity due to the inherent cross-reactivity of TCR-peptide-MHC interactions [2, 5].

Other names

T-cell receptor alpha-beta complexTCR alpha/betaT-cell antigen receptor alpha-betaTCRab

T-cell redirection, T-cell activation, Immunosuppression, Antigen-specific cytotoxicity