T cell receptor

Information about T cell receptor

T cell receptor alpha locus
Identifiers
Symbol(s)	TRA@ TCRA
Entrez	6955
OMIM	186880

T cell receptor beta locus
Identifiers
Symbol(s)	TRB@ TCRB
Entrez	6957
OMIM	186930

Antigen presentation stimulates T cells to become either "cytotoxic" CD8+ cells or "helper" CD4+ cells.

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 generally 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.

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 both the TCR α-chain and β-chain have three hypervariable or complementarity determining regions (CDRs), while the variable region of the β-chain has an additional area of hypervariability(HV4) that does not normally contact antigen and therefore is not considered a CDR.

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.

The constant domain of the TCR domain consists of short connecting sequences in which a cysteine residue forms disulfide bonds which forms a lin between the two chains.

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 p3n15) 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 N- and P- nucleotide additions, which accounts for the great diversity in specificity of the T cell receptor for processed antigen.

The TCR Complex

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

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.

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.

References

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

External links

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

Chemistry

The molecules in a dimer are connected by covalent bonds or weaker interactions such as hydrogen bonds.
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γδ T cells represent a small subset of T cells that possess a distinct T cell receptor (TCR) on their surface. A majority of T cells have a TCR composed of two glycoprotein chains called α- and β- TCR chains.
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immunoglobulin superfamily (IgSF) is a large group of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. Molecules are categorized as members of this superfamily based on shared structural features with immunoglobulins
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complementarity determining region (CDR) is a short amino acid sequence found in the variable domains of antigen receptor (e.g. immunoglobulin and T cell receptor) proteins that complements
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Antigen processing is a biological process that prepares antigens for presentation to special cells of the immune system called T lymphocytes. This process involves two distinct pathways for processing of antigens from an organism's own (self) proteins or intracellular pathogens (e.
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The N-terminus (also known as the amino-terminus, NH₂-terminus, N-terminal end or amine-terminus) refers to the end of a protein or polypeptide terminated by an amino acid with a free amine group (-NH₂).
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The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal end, or COOH-terminus) of a protein or polypeptide is the end of the amino acid chain terminated by a free carboxyl group (-COOH).
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Superantigens (SAgs) are secreted proteins (exotoxins) that exhibit highly potent lymphocyte-transforming (mitogenic) activity directed towards T lymphocytes [2,4,6]. Compared to a normal antigen-induced T-cell response where .001-.
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B cells are lymphocytes that play a large role in the humoral immune response as opposed to the cell-mediated immune response that is governed by T cells. The principal function of B cells is to make antibodies against soluble antigens.
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Antibodies (also known as immunoglobulins) are proteins that are found in blood or other bodily fluids of vertebrates, and are used by the immune system to identify and neutralize foreign objects, such as bacteria and viruses.
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V(D)J recombination is a mechanism of DNA recombination that occurs in vertebrates, which randomly selects and assembles segments of genes encoding specific proteins with important roles in the immune system.
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palindrome is a word, phrase, number or other sequence of units that has the property of reading the same in either direction (the adjustment of punctuation and spaces between words is generally permitted). Composing literature in palindromes is an example of constrained writing.
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amino acid is a molecule that contains both amine and carboxyl functional groups. In biochemistry, this term refers to alpha-amino acids with the general formula H₂NCHRCOOH, where R is an organic substituent.
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Identifiers
Symbol CD3E

Entrez 916
HUGO 1674
OMIM 186830

RefSeq NM_000733
UniProt P07766
Other data

Locus Chr. 11 q23

CD3g molecule, gamma (CD3-TCR complex)

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A transmembrane protein is a protein that spans the entire biological membrane. Transmembrane proteins aggregate and precipitate in water. They require detergents or nonpolar solvents for extraction, although some of them (beta-barrels) can be also extracted using denaturing agents.
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Cytoplasm is a gelatinous, semi-transparent fluid that fills most cells. Eukaryotic cells contain a nucleus that is kept separate from the cytoplasm by a double membrane layer. The cytoplasm has three major elements; the cytosol, organelles and inclusions.
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A co-receptor is a second cell surface receptor required for the entry of a pathogen into a host cell or initiation of a biological process. It is also a protein that increases the sensitivity of an antigen receptor to its antigen by binding to other ligands.
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T helper cells (also known as effector T cells or T_h cells) are a sub-group of lymphocytes (a type of white blood cell or leukocyte) that plays an important role in establishing and maximizing the capabilities of the immune system.
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CD4 (cluster of differentiation 4) is a glycoprotein expressed on the surface of T helper cells, regulatory T cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 (after the OKT4 monoclonal antibody that
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MHC Class II molecules are found only on a few specialized cell types, including macrophages, dendritic cells and B cells, all of which are professional antigen-presenting cells (APCs).
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cytotoxic T cell (also known as T_C, CTL, T-Killer cell or killer T cell) belongs to a sub-group of T lymphocytes (a type of white blood cell) which are capable of inducing the death of infected somatic or tumor cells; they kill cells that are infected with
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Identifiers
Symbol CD8B
Alt. Symbols CD8B1

Entrez 926
HUGO 1707
OMIM 186730

RefSeq NM_172099
UniProt P10966
Other data

Locus Chr.
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MHC class I molecules are found on almost every nucleated cell of the body. Because MHC class I molecules present peptides derived from cytosolic proteins, the pathway of MHC class I presentation is often called the cytosolic or endogenous pathway.
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• • [ e] Transmembrane receptors: immune receptors
Cytokine receptor	Type I: interleukin (IL-2, IL-3) - CSF (Erythropoietin, GM-CSF, G-CSF) - Glycoprotein 130/Oncostatin M - Leukemia inhibitory factor - common subunits (Common gamma chain, CSF2RB) Type II: interleukin (IL22RA2) - interferon (IFNAR, IFNGR) Other: Chemokine - TGF-beta - Tumor necrosis factor
Pattern recognition/Toll-like	TLR 1 - TLR 2 - TLR 3 - TLR 4 - TLR 5 - TLR 6 - TLR 7 - TLR 8 - TLR 9 - TLR 10
Fc receptor	ε (FcεRI, FcεRII) - γ (FcγRI, FcγRII, FcγRIII) - α/μ (FcαRI, Fcα/μR) - Neonatal
Lymphocyte homing receptor	CD44 - L-selectin - VLA-4 - LFA-1
other	Antigen receptor (B-cell, T cell) - Complement - Formyl peptide - Immunophilins - Integrin - Killer-cell immunoglobulin-like - Scavenger

• • [ e] The T cell receptor complex
The antigen receptor	TCR \| TCRα \| TCRβ \| TCRγ \| TCRδ
Accessory molecules	CD3 \| CD3γ \| CD3δ \| CD3ε \| ζ-chain (also called CD3ζ and TCRζ)
Co-receptors	CD8 (with two glycoprotein chains CD8α and CD8β) \| CD4
Ligands	MHC (MHC class I and MHC class II)

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