T-cell Receptor (TCR)

  • The T-cell Receptor (TCR) is a multi-subunit protein structure present on the membrane of T-cells which can recognize, with high specificity, a peptide of a particular sequence bound to an MHC molecule. Because each TCR can recognize only one sequence of short peptide, millions of different TCRs exist, each with a different specificity for a particular peptide. As described on the MHC page, MHC proteins non-specifically bind and display short peptides derived from the random degradation of proteins from the intracellular or extracellular environments. TCRs are generated to recognize only those peptides which are derived from microbial sources and in doing so allow T-cells to distinguish whether a microbial infection is taking place within the intracellular or extracellular environment. In this page we solely discuss the structural features of the T-cell Receptor and how those structural features allow distinction between different peptide sequences when attached to MHC. How and when TCRs are synthesized is discussed further in T-cell Development and how the TCR is utilized in the context of an immune response is discussed in Cell-mediated Immunity.
Basic Structure
  • The TCR is composed of two membrane protein subunits known as alpha and beta which dimerize on the surface of T-cells and are covalently linked by a disulfide bond. The overall structure of a TCR is highly similar to an isolated antibody Fab Fragment with the outer half consisting of a variable region and the inner half consisting of a constant region. The variable region possess a different sequence from one TCR to another and accounts for the capacity of TCRs to recognize different peptides. The most sequence variability between TCRs occurs at the TCR peptide-binding cleft which exists at the tip of the TCR where contact with the MHC-peptide complex occurs. Importantly, TCRs can only bind foreign peptides when they are in complex with MHC, this is in contrast to Antibodies which can bind free-floating antigens.
  • Unlike Antibody, there are not other physiologically important subtypes of TCR. Consequently, all T-cells possess TCRs with the same overall structure (Although their precise sequences will be different in the variable region, consistent with different antigen-specificities)
  • FYI: There do exist TCRs composed of two alternative gamma and delta TCR chains; however, the proportion of T-cells with these alternative TCRs is quite small and their physiological significance is not well-understood and probably not critical for most types of immunity