The T cell receptor (TCR) is an antigen receptor molecule on the surface of T cells, responsible for the recognition of antigen presented to T cells by MHC molecules leading potentially to the activation of the T cell and an immune response to the antigen. The T cell receptor is a heterodimer consisting of two transmembrane glycoprotein chains, the α and β chains (there are also a small proportion of γδ chains) each with two domains, which are linked by a disulphide bond.
The TCR bears some structural similarity to the Fab fragment of an antibody molecule. The α and β chains each posses a constant (C) domain proximal to the cell membrane and a variable (V) domain distal from the membrane. This gives a Vα and Cα domain for the α chain and a Vβ and Cβ domain for the β chain. The variable and constant domains of the α chain dimerise with the variable and constant domains of the β chain. All domains adopt the classical immunoglobulin fold with two anti-parallel β-sheets adopting a Greek key motif held together into a ‘sandwich’ by a disulphide bond. The Cα domain does differ a little in having part of the β sheet replaced by loosely packed strands and a short segment of α helix. Like the variable region of the Fab fragment of antibodies, the variability of amino acids in the V region of the TCR is not evenly distributed throughout the sequence but is concentrated into hypervariable regions which code for the hypervariable loops. These are brought together by the α and β chain at the tip of the TCR to form the Complementarity Determining Regions (CDRs) which make contact with the MHC. The alignment of the TCR CDRs differs slightly from those of antibody molecules. The Vα CDR2 loop for instance is oriented roughly at 90 degrees for the equivalent antibody CDR. The Vβ domain includes a fourth hypervariable region which does not have an equivalent in antibodies.
The short cytoplasmic tail of the TCR means it cannot directly signal when it binds to a peptide-MHC complex. Instead the TCR is associated on the cell membrane with a group of non polymorphic signalling molecules collectively called CD3 which transmit an intracellular signal when the TCR binds to a peptide-MHC complex. CD3 is made up of one γ and δ and two ε molecules which all have in their extracellular domains some limited sequence homology to the immunoglobulin domain. These molecules have small cytoplasmic domains and transmembrane domains with negatively charged residues. In the membrane, these negatively charged residues form salt bridges with the positively charged residues in the transmembrane region of the TCR. The TCR-CD3 receptor complex is completed by two other invariant proteins ζ and η which form dimmers linked by disulphide bonds. At the T cell surface therefore, the TCR-CD3 complex is expressed as an αβ (or γδ) heterodimer, in association with CD3γε and CD3δε dimmers with an intracellular ζζ homodimers or a ζη heterodimer.
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