T-cell receptor

Complex of proteins that is localized on the surface of T cells and serves to recognize antigens. These are presented by major histocompatibility complexes ( MHC) (see also under T-cell receptor genes) (see also the special features of T-cell activation by superantigens).

The T-cell receptor occurs in two versions: as an alpha/beta receptor and as a gamma/delta receptor. The alpha/beta receptor is much more common (95%). The TCR consists of two chains (alpha/beta or delta/gamma), each of which is composed of a constant domain (C) and a variable domain (V). The constant domain faces the cell membrane and penetrates it with two short cytoplasmic extensions. This serves to anchor the receptor.

The variable domain of the alpha chain has 3 complimentarity determining regions (CDRs), whereas the beta chain has 4 CDRs (note: the alpha chain is similar to the light chain of immunoglobulins, the beta chain to the Fab fragment of the heavy chain). The genes coding for the protein chains are located on 2 chromosomes. The genes for the alpha and delta chains are located on chromosome 14, the genes for the beta and gamma chains on chromosome 7.

Remark: A crucial event for the activation of the TCR complex is the activation of the enzyme phospholipase C γ-1, which in turn leads to the activation of the three most important signaling pathways that drive T cell activation:

• the MAP kinase pathway
• the protein kinase C pathway and
• the calcineurin pathway.

These pathways culminate in the activation of the transcription factors NF-κB, NFAT and AP-1, which initiate gene transcription and lead to the differentiation, proliferation and effector activity of T cells.

The lock-and-key principle applies to antigen binding, i.e. if the structure of a presented antigen matches the structure of the TCR, binding occurs. The signal resulting from the binding is amplified by simultaneous binding to co-receptors. Examples of TCRs are the CD4 and CD8 receptors(see CD classification below). The CD4 receptor exclusively binds MHC II, while the CD8 receptor is specific for MHC I. The co-receptors are not only responsible for the specificity of the TCR but also for a firm binding between the antigen-presenting cell and the T cell.

Note: The large variety of specific T cell receptors would exceed the size of a genome if a separate gene existed for every conceivable receptor. This diversity is realized by the fact that the individual gene segments are present in several copies before rearrangement, which can be combined with each other in the manner of a combination lock during the maturation of the lymphocytes.

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