T-cell receptor

Complex of proteins localized on the surface of T cells and serving the recognition of antigens. These are presented by major histocompatibility complexes ( MHC) (see also under T cell receptor genes (see also the specifics of T cell activation by superantigens).

The T cell receptor exists in two versions: as alpha/beta receptor and as gamma/delta receptor. The alpha/beta receptor is much more abundant (95%). The TCR is composed of two chains (alpha/beta or delta/gamma), each in turn 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 resembles the immunoglobulin light chain, the beta chain resembles 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, and the genes for the beta and gamma chains are located on chromosome 7.

Remark:

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

• the Ras-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 T cell differentiation, proliferation, and effector activity.

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 binding is amplified by simultaneous binding to co-receptors. Examples of TCR`s are the CD4 and CD8 receptor (see CD classification below). The CD4 receptor binds exclusively MHC II, while the CD8 receptor is specific for MHC I. The co-receptors are not only responsible for specificity of the TCR but also for a tight binding between the antigen presenting cell and the T cell.

Note: The great diversity of specific T cell receptors would exceed the size of a genome if there were a separate gene 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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7. Prasad A et al (2016) Identification of gene mutations and fusion genes in patients with Sézary Syndrome. J Invest Dermatol. doi: 10.1016/y.y.y.i.d.2016.03.024.