T cell receptor

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The two chains of the T cell receptor

The T cell receptor or TCR is a molecule found on the surface of T lymphocytes (or T cells) that is responsible for recognizing antigens bound to major histocompatibility complex (MHC) molecules. It is a heterodimer consisting of an alpha and beta chain in 95% of T cells, while 5% of T cells have TCRs consisting of gamma and delta chains. Engagement of the TCR with antigen and MHC results in activation of its T lymphocyte through a series of biochemical events mediated by associated enzymes, co-receptors and specialized accessory molecules.

[edit] Structural characteristics of the TCR

Each chain of the TCR is a member of the immunoglobulin superfamily and possesses one N-terminal immunoglobulin (Ig)-variable (V) domain, one Ig-constant (C) domain, a transmembrane/cell membrane-spanning region and a short cytoplasmic tail at the C-terminal end. The variable domain of the TCR α-chain has three hypervariable or complementarity determining regions (CDRs), while the variable region of the β-chain has four CDRs. CDR3 is the main CDR responsible for recognizing processed antigen, although CDR1 of the alpha chain has also been shown to interact with the N-terminal part of the antigenic peptide while CDR1 of the beta chain interacts with the C-terminal part of the peptide. CDR2 is thought to recognize the MHC. CDR4 of the β-chain is not thought to participate in antigen recognition, but has been shown to interact with superantigens.

[edit] Generation of the TCR

Processes for TCR formation are similar to those described for B-cell antigen receptors, otherwise known as immunoglobulins. The TCR alpha chain is generated by VJ recombination while the beta chain is generated by V(D)J recombination (both involve a somewhat random joining of gene segments to generate the complete TCR chain). Similarly, generation of the TCR gamma chain involves VJ recombination while generation of the TCR delta chain occurs by V(D)J recombination. The intersection of these specific regions (V and J for the alpha or gamma chain, V D and J for the beta or delta chain) corresponds to the CDR3 region that is important for antigen-MHC recognition (see above). Furthermore, it is the unique combination of the segments at this region, along with palindromic and random nucleotide additions, which accounts for the great diversity in specificity of the T cell receptor for processed antigen.

[edit] The TCR complex

The transmembrane region of the TCR is composed of positively charged amino acids. It is thought that this allows the TCR to associate with other molecules like CD3, that possess three distinct chains (γ, δ and ε) in mammals and the ζ-chain. These accessory molecules have negatively charged transmembrane regions and are vital to propagating the signal from the TCR into the cell; the cytoplasmic tail of the TCR is extremely short, making it unlikely to participate in signaling. The CD3- and ζ-chains, together with the TCR, form what is known as the T cell receptor complex.

The T-cell receptor complex with TCR-α and TCR-β chains, CD3 and ζ-chain accessory molecules and the co-receptor CD4

[edit] TCR co-receptors

The signal from the T cell complex is enhanced by simultaneous binding of the MHC molecules by a specific co-receptor. On helper T cells, this co-receptor is CD4 that exclusively binds the class II MHC. On cytotoxic T cells, this co-receptor is CD8 that is specific for class I MHC. The co-receptor not only ensures the specificity of the TCR for the correctly presented antigen, it also allows prolonged engagement between the antigen presenting cell and the T cell and recruits essential molecules (e.g. LCK) inside the cell that are involved in the signaling of that activated T lymphocyte.

[edit] References

1. Janeway CA, Jr. et al (2005). Immunobiology., 6th ed., Garland Science. ISBN 0-443-07310-4. 
2. Abbas AK and Lichtman AH (2003). Cellular and Molecular Immunology, 5th ed., Saunders, Philadelphia. ISBN 0-7216-0008-5. 

[edit] External links

• UMich Orientation of Proteins in Membranes protein/pdbid-2hac - Calculated spatial position of Zeta-zeta dimer of T cell receptor in membrane
• MeSH T-Cell+Receptor

[edit] See also

• T cell
• Co-stimulation