CD3 (immunology)

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
Symbol	CD3D
Alt. symbols	T3D
NCBI gene	915
HGNC	1673
OMIM	186790
PDB	1XIW
RefSeq	NM_000732
UniProt	P04234
Other data
Locus	Chr. 11 q23
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CD3e molecule, epsilon
Identifiers
Symbol	CD3E
NCBI gene	916
HGNC	1674
OMIM	186830
RefSeq	NM_000733
UniProt	P07766
Other data
Locus	Chr. 11 q23
Search for Structures Swiss-model Domains InterPro

CD3g molecule, gamma
Identifiers
Symbol	CD3G
NCBI gene	917
HGNC	1675
OMIM	186740
RefSeq	NM_000073
UniProt	P09693
Other data
Locus	Chr. 11 q23
Search for Structures Swiss-model Domains InterPro

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.

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.

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

• CD3+Antigens at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• Mouse CD Antigen Chart
• Human CD Antigen Chart