![]() The TCR is a disulfide-linked membrane-anchored heterodimeric protein normally consisting of the highly variable alpha (α) and beta (β) chains expressed as part of a complex with the invariant CD3 chain molecules. This allowed scientists from around the world to carry out studies on the TCR, leading to important studies in the fields of CAR-T, cancer immunotherapy and checkpoint inhibition. These findings allowed the entity and structure of the elusive TCR, known before as the "Holy Grail of Immunology", to be revealed. Davis identified the cDNA clones encoding the human and mouse TCR respectively in 1984. In 1983, Ellis Reinherz first defined the structure of the human T cell receptor using anti-idiotypic monoclonal antibodies to T cell clones, complemented by studies in the mouse by Pippa Marrack and John Kappler. Allison first discovered a clonally expressed T cell surface epitope in murine T-lymphoma. Based on the initial receptor triggering mechanism, the TCR belongs to the family of non-catalytic tyrosine-phosphorylated receptors (NTRs). ![]() When the TCR engages with antigenic peptide and MHC (peptide/MHC), the T lymphocyte is activated through signal transduction, that is, a series of biochemical events mediated by associated enzymes, co-receptors, specialized adaptor molecules, and activated or released transcription factors. Each locus can produce a variety of polypeptides with constant and variable regions. Orthologues of the 4 loci have been mapped in various species. This ratio changes during ontogeny and in diseased states (such as leukemia). In humans, in 95% of T cells the TCR consists of an alpha (α) chain and a beta (β) chain (encoded by TRA and TRB, respectively), whereas in 5% of T cells the TCR consists of gamma and delta (γ/δ) chains (encoded by TRG and TRD, respectively). ![]() The TCR is composed of two different protein chains (that is, it is a hetero dimer). The binding between TCR and antigen peptides is of relatively low affinity and is degenerate: that is, many TCRs recognize the same antigen peptide and many antigen peptides are recognized by the same TCR. 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. Antigen presentation stimulates T cells to become either "cytotoxic" CD8+ cells or "helper" CD4+ cells. ![]()
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