The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The TCR is composed of two different protein chains, and in humans, in 95% of T cells, the TCR consists of an alpha (α) chain and a beta (β) chain, whereas in 5% of T cells, the TCR consists of gamma and delta (γ/δ) chains. The TCR is a member of the immunoglobulin superfamily, a large group of proteins involved in binding, recognition, and adhesion.
TCR-mediated T cell activation involves both the canonical (classical) and the non-canonical (alternative) NF-κβ pathway. Dysregulation of TCR signaling can lead to anergy or autoimmunity. The core TCR complex consists of two TCR chains and six cluster of differentiation 3 (CD3) chains, and several other components include coreceptors, kinases, and ligands. TCR activation leads to activation of proximal and distal signaling pathways, and productive T cell activation also involves the engagement of additional cell surface receptors, i.e., co-stimulatory molecules like CD28.
TCR-based therapy employs genetically modified lymphocytes that are directed against specific tumor markers. The majority of TCR structures are heterodimers comprised of α- and β-chains that are covalently linked via a disulfide bond between the conserved cysteine residues located within the constant region of each chain. Tumor markers used for TCR-based therapy, their functions, and the tumor types associated with their overexpression are listed in Table 3.
In summary, the T-cell receptor (TCR) is a protein complex found on the surface of T cells that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The TCR is composed of two different protein chains, and its activation leads to activation of proximal and distal signaling pathways. TCR-based therapy employs genetically modified lymphocytes that are directed against specific tumor markers.
