CD3 (
cluster of differentiation
The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophen ...
3) is a
protein complex
A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain.
Protein ...
and
T cell co-receptor that is involved in activating both the
cytotoxic T cell
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular ...
(CD8+ naive T cells) and
T helper cells (CD4+ naive T cells). It 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 the
T-cell receptor
The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The bindin ...
(TCR) and the
CD3-zeta (ζ-chain) to generate an activation signal in
T lymphocytes. The TCR, CD3-zeta, and the other 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.
A structure of the extracellular and transmembrane regions of the CD3γε/CD3δε/CD3ζζ/TCRαβ complex was solved with
CryoEM, showing for the first time how the CD3 transmembrane regions enclose the TCR transmembrane regions in an open barrel.
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 CD3γ, CD3ε, and CD3δ molecules each 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 tail of CD3ζ contains 3 ITAM motifs.
Regulation
Phosphorylation of the
ITAM on CD3 renders the CD3 chain capable of binding an
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...
called
ZAP70 (zeta associated protein), a
kinase
In biochemistry, a kinase () is an enzyme that catalysis, catalyzes the transfer of phosphate groups from High-energy phosphate, high-energy, phosphate-donating molecules to specific Substrate (biochemistry), substrates. This process is known as ...
that is important in the signaling cascade of the T cell.
As a drug target
Because CD3 is required for
T cell activation
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell ...
, drugs (often
monoclonal antibodies) that target it are being investigated as
immunosuppressant therapies (e.g.,
otelixizumab,
teplizumab) for
type 1 diabetes and other
autoimmune diseases.
As a drug target in cancer research
New anticancer drug treatments are being developed based upon the CD3 T cell co-receptor, with molecules being designed for altering the co-stimulatory signal to help get the T-cell to recognize the cancer cell and become fully activated. Cancers that possess the B7-H3 immunoregulatory checkpoint receptor on the tumor cell have been one such target in clinical trials. This B7-H3 protein is expressed on cancer cell for several types of cancer. Often, the drug will contain two domains, one binding the T-cell's CD3 and the other targeting and binding cancer cells.
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 cell
Purkinje cells, or Purkinje neurons, are a class of GABAergic inhibitory neurons located in the cerebellum. They are named after their discoverer, Czech anatomist Jan Evangelista Purkyně, who characterized the cells in 1839.
Structure
The ...
s.
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
leukaemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
s, and can therefore be used to distinguish them from superficially similar
B-cell and
myeloid neoplasms.
References
Further reading
*
External links
*
*
Mouse CD Antigen Chart
{{DEFAULTSORT:Cd3 (Immunology)
Clusters of differentiation
T cells
Immunology