In immunology, the CD3 T-cell co-receptor
is 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 and the ζ-chain to
generate an activation signal in T lymphocytes.
The TCR, ζ-chain, and CD3 molecules together
comprise 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.
Regulation
Phosphorylation of the ITAM on CD3 renders
the CD3 chain capable of binding an enzyme
called ZAP70, 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 that target it are being investigated
as immunosuppressant therapies 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.
References
Further reading
External links
CD3 Antigens at the US National Library of
Medicine Medical Subject Headings
Mouse CD Antigen Chart
Human CD Antigen Chart
