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[[Image:TCR_complex.jpg|thumb|250px|right|The ''[[T-cell receptor]] complex'' with TCR-α and TCR-β chains, [[CD3]] and ζ-chain accessory molecules and the co-receptor [[CD4]]]]
[[Image:TCRComplex.png|thumb|237px|right|The ''[[T-cell receptor]] complex'' with TCR-α and TCR-β chains (top), ζ-chain accessory molecules (bottom) and ''CD3'' (represented by [[CD3G|CD3γ]], [[CD3D|CD3δ]] and two [[CD3E|CD3ε]]).]]
{{protein
{{infobox protein
| Name = CD3d molecule, delta (CD3-TCR complex)
| Name = [[CD3D|CD3d molecule, delta]]
| caption =  
| caption =  
| image =  
| image =  
| width = 180px
| width = 180px
| HGNCid = 1673
| HGNCid = 1673
| Symbol = CD3D  
| Symbol = [[CD3D]]
| AltSymbols = T3D
| AltSymbols = T3D
| EntrezGene = 915
| EntrezGene = 915
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| LocusSupplementaryData =  
| LocusSupplementaryData =  
}}
}}
{{protein
{{infobox protein
| Name = CD3e molecule, epsilon (CD3-TCR complex)
| Name = [[CD3E|CD3e molecule, epsilon]]
| caption =  
| caption =  
| image =  
| image =  
| width = 180px
| width = 180px
| HGNCid = 1674
| HGNCid = 1674
| Symbol = CD3E  
| Symbol = [[CD3E]]
| AltSymbols =
| AltSymbols =
| EntrezGene = 916
| EntrezGene = 916
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| LocusSupplementaryData =  
| LocusSupplementaryData =  
}}
}}
{{protein
{{infobox protein
| Name = CD3g molecule, gamma (CD3-TCR complex)
| Name = [[CD3G|CD3g molecule, gamma]]
| caption =  
| caption =  
| image =  
| image =  
| width = 180px
| width = 180px
| HGNCid = 1675
| HGNCid = 1675
| Symbol = CD3G  
| Symbol = [[CD3G]]
| AltSymbols =  
| AltSymbols =  
| EntrezGene = 917
| EntrezGene = 917
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| LocusSupplementaryData =  
| LocusSupplementaryData =  
}}
}}
{{SI}}
In [[immunology]], the '''CD3''' ('''[[cluster of differentiation]] 3''') T-cell co-receptor helps to activate both the cytotoxic T-Cell (CD8+ naive T cells) and also T helper cells (CD4+ naive T cells). It consists of a protein complex and is composed of four distinct chains. In mammals, the complex contains a [[CD3G|CD3γ]] chain, a [[CD3D|CD3δ]] chain, and two [[CD3E|CD3ε]] chains. These chains associate with a molecule known as the [[T-cell receptor]] (TCR) and the [[ζ-chain]] (zeta-chain) to generate an activation signal in [[T lymphocytes]]. The TCR, ζ-chain, and CD3 molecules together constitute the TCR complex.
{{CMG}}


==Structure==
The CD3γ, CD3δ, and CD3ε chains are highly related cell-surface proteins of the [[immunoglobulin superfamily]] containing a single [[extracellular]] immunoglobulin domain.


Containing aspartate residues, the transmembrane region of the CD3 chains is negatively charged, a characteristic that allows these chains to associate with the positively charged TCR chains.<ref name="isbn1-4292-0211-4">{{cite book |author1=Kuby, Janis |author2=Kindt, Thomas J. |author3=Goldsby, Richard A. |author4=Osborne, Barbara A. | title = Kuby immunology | edition = | language = | publisher = W.H. Freeman | location = San Francisco | year = 2007 | origyear = | pages = | quote = | isbn = 1-4292-0211-4 | oclc = | doi = | url = | accessdate = }}</ref>


In [[immunology]], the '''CD3''' [[antigen]] (CD stands for [[cluster of differentiation]]) is a protein complex composed of four distinct chains ([[CD3G|CD3γ]], [[CD3D|CD3δ]] and two times [[CD3E|CD3ε]]) in mammals, that associate with molecules known as the [[T cell receptor]] (TCR) and the [[ζ-chain]] to generate an activation signal in [[T lymphocytes]].
The intracellular tails of the CD3 molecules contain a single conserved motif known as an ''[[immunoreceptor tyrosine-based activation motif]]'' or ITAM for short, which is essential for the signaling capacity of the TCR.


The TCR, ζ-chain and CD3 molecules together comprise the TCR complex.
The intracellular tails of the ζ chain contain 3 ITAM motifs.


The CD3γ, CD3δ and CD3ε chains are highly related cell surface proteins of the [[immunoglobulin superfamily]] containing a single [[extracellular]] immunoglobulin domain.
==Regulation==
[[Phosphorylation]] of the ITAM on CD3 renders the CD3 chain capable of binding an [[enzyme]] called [[ZAP70]] (zeta associated protein), a [[kinase]] that is important in the signaling cascade of the T cell.


The transmembrane region of the CD3 chains is negatively charged, a characteristic that allows these chains to associate with the positively charged TCR chains ([[TCRα]] and [[TCRβ]]).
==As a drug target==
Because CD3 is required for [[T-cell activation]], drugs (often [[monoclonal antibodies]]) that target it are being investigated as [[immunosuppressant]] therapies (e.g., [[otelixizumab]]) for [[type 1 diabetes]] and other [[autoimmune disease]]s.


The intracellular tails of the CD3 molecules contain a single conserved motif known as an ''[[immunoreceptor tyrosine-based activation motif]]'' or ITAM for short, which is essential for the signaling capacity of the TCR.
==Immunohistochemistry==
CD3 is initially expressed in the cytoplasm of pro-thymocytes, the [[stem cell]]s from which T-cells arise in the [[thymus]]. The pro-thymocytes differentiate into common [[thymocyte]]s, and then into medullary thymocytes, and it is at this latter stage that CD3 antigen begins to migrate to the cell membrane. The antigen is found bound to the membranes of all mature T-cells, and in virtually no other cell type, although it does appear to be present in small amounts in [[Purkinje cell]]s.


[[Phosphorylation]] of the ITAM on CD3 renders the CD3 chain capable of binding an [[enzyme]] called [[ZAP70]] (zeta associated protein), a [[kinase]] that is important in the signaling cascade of the T cell.  
This high specificity, combined with the presence of CD3 at all stages of T-cell development, makes it a useful [[immunohistochemistry|immunohistochemical]] marker for T-cells in tissue sections. The antigen remains present in almost all T-cell [[lymphoma]]s and [[leukaemia]]s, and can therefore be used to distinguish them from superficially similar [[B-cell]] and [[myeloid cell|myeloid]] [[neoplasm]]s.<ref name=Leong>{{cite book|author=Leong, Anthony S-Y|author2=Cooper, Kumarason|author3=Leong, F Joel W-M|year=2003|title=Manual of Diagnostic Cytology|edition=2|publisher=Greenwich Medical Media, Ltd.|pages=63–64|isbn=1-84110-100-1}}</ref>


==References==
== References ==
* Cellular and Molecular Immunology (5th Ed.) Abbas AK, and Lichtman, Editor: Saunders, Philadelphia, 2003.
{{Reflist}}
 
== Further reading ==
{{refbegin}}
* {{cite book |author1=Shiv Pillai MD |author2=Abul K. Abbas MBBS |author3=Andrew Wilson | title = Cellular and Molecular Immunology: with STUDENT CONSULT Online Access | edition = | language = | publisher = Saunders | location = Philadelphia | year = 2011 | origyear = | pages = | quote = | isbn = 1-4377-1528-1 | oclc = | doi = | url = | accessdate = }}
{{refend}}


==External links==
==External links==
* {{MeshName|CD3+Antigens}}
* {{MeshName|CD3+Antigens}}
* [http://www.ebioscience.com/ebioscience/whatsnew/mousecdchart.htm Mouse CD Antigen Chart]
* [http://www.ebioscience.com/resources/human-cd-chart.htm Human CD Antigen Chart]


{{T cell receptor}}
{{T cell receptor}}
{{Clusters of differentiation}}
{{Clusters of differentiation}}
{{Clusters of differentiation by lineage}}


 
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Revision as of 08:51, 1 May 2017

File:TCRComplex.png
The T-cell receptor complex with TCR-α and TCR-β chains (top), ζ-chain accessory molecules (bottom) and CD3 (represented by CD3γ, CD3δ and two CD3ε).
CD3d molecule, delta
Identifiers
SymbolCD3D
Alt. symbolsT3D
Entrez915
HUGO1673
OMIM186790
PDB1XIW
RefSeqNM_000732
UniProtP04234
Other data
LocusChr. 11 q23
CD3e molecule, epsilon
Identifiers
SymbolCD3E
Entrez916
HUGO1674
OMIM186830
RefSeqNM_000733
UniProtP07766
Other data
LocusChr. 11 q23
CD3g molecule, gamma
Identifiers
SymbolCD3G
Entrez917
HUGO1675
OMIM186740
RefSeqNM_000073
UniProtP09693
Other data
LocusChr. 11 q23

In immunology, the CD3 (cluster of differentiation 3) T-cell co-receptor helps to activate both the cytotoxic T-Cell (CD8+ naive T cells) and also T helper cells (CD4+ naive T cells). It consists of a protein complex and is composed of four distinct chains. In mammals, the complex contains a CD3γ chain, a CD3δ chain, and two CD3ε chains. These chains associate with a molecule known as the T-cell receptor (TCR) and the ζ-chain (zeta-chain) to generate an activation signal in T lymphocytes. The TCR, ζ-chain, and CD3 molecules together constitute the TCR complex.

Structure

The CD3γ, CD3δ, and CD3ε chains are highly related cell-surface proteins of the immunoglobulin superfamily containing a single extracellular immunoglobulin domain.

Containing aspartate residues, the transmembrane region of the CD3 chains is negatively charged, a characteristic that allows these chains to associate with the positively charged TCR chains.[1]

The intracellular tails of the CD3 molecules contain a single conserved motif known as an immunoreceptor tyrosine-based activation motif or ITAM for short, which is essential for the signaling capacity of the TCR.

The intracellular tails of the ζ chain contain 3 ITAM motifs.

Regulation

Phosphorylation of the ITAM on CD3 renders the CD3 chain capable of binding an enzyme called ZAP70 (zeta associated protein), a kinase that is important in the signaling cascade of the T cell.

As a drug target

Because CD3 is required for T-cell activation, drugs (often monoclonal antibodies) that target it are being investigated as immunosuppressant therapies (e.g., otelixizumab) for type 1 diabetes and other autoimmune diseases.

Immunohistochemistry

CD3 is initially expressed in the cytoplasm of pro-thymocytes, the stem cells from which T-cells arise in the thymus. The pro-thymocytes differentiate into common thymocytes, and then into medullary thymocytes, and it is at this latter stage that CD3 antigen begins to migrate to the cell membrane. The antigen is found bound to the membranes of all mature T-cells, and in virtually no other cell type, although it does appear to be present in small amounts in Purkinje cells.

This high specificity, combined with the presence of CD3 at all stages of T-cell development, makes it a useful immunohistochemical marker for T-cells in tissue sections. The antigen remains present in almost all T-cell lymphomas and leukaemias, and can therefore be used to distinguish them from superficially similar B-cell and myeloid neoplasms.[2]

References

  1. ↑ Kuby, Janis; Kindt, Thomas J.; Goldsby, Richard A.; Osborne, Barbara A. (2007). Kuby immunology. San Francisco: W.H. Freeman. ISBN 1-4292-0211-4.
  2. ↑ Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 63–64. ISBN 1-84110-100-1.

Further reading

  • Shiv Pillai MD; Abul K. Abbas MBBS; Andrew Wilson (2011). Cellular and Molecular Immunology: with STUDENT CONSULT Online Access. Philadelphia: Saunders. ISBN 1-4377-1528-1.

External links

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