CD3 CD3α, β, δ, ε, η, γ, TCR ζ (now CD247), T3, For individual information See CDδ, ε and γ.
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Lineage Restricted Molecule
Type 1 glycoprotein
T Cell

Expression
CD3 is expressed during thymopoiesis and on mature ab and gd T cells in the periphery.  The majority of T cells express the ab TCR.  Less than 10% of human peripheral T cells express the gd TCR complex.  In the mouse the majority on T cells present in some epithelial tissues are gd+ and have limited receptor diversity.  Pre-TCRa (pTCRa ) is expressed on immature but not mature T cells.  In contrast, a large subpopulation of gd TCR+ T cell is present in ruminants and pigs.  In cattle, it is characterized by the expression of WC1, as a member of the scavenger receptor cysteine-rich super familiy of molecules that includes CD5, CD6, and CD163.  In pigs, it is characterized by expression  of the orthologue of WC1. 



Structure
MOLECULAR FAMILY NAME: Belongs to the immunoglobulin supergene family.

CD3 is a multigene cell-surface receptor structure consisting of constant components CD3-γ,δ,ε,ζ (and in mouse η).  CD3/TCR consists of both IgSF and non-IgSF proteins.  The CD3/TCR contains a TCR heterodimer, 2 e chains , 1 g and 1 d chain and 1 z homodimer or the  zh heterodimer.  The ab and gd heterodimers are clonotypic and consist of Ig-like variable and constant domains.  The ab heterodimer has been crystallized and the structure confirms the predicted IgSF domains.  In immature T cells, pTCRa which is comprised of 1 conserved IgSF domain in its extracellular region is expressed instead of TCRa.  The transmembrane domains of the clonotypic and invariant chains contain oppositely charged aa.  The z chain forms disulfide-linked homodimers or, less frequently, heterodimers with its splicing variant, the h chain.  The z chain is related to the g chain of the IgE Fc receptor and can also associate with the Fc receptor CD16.  The cytoplasmic domains of the CD3 and z chain contain ITAM motifs.  CD3ζ has been designated as CD247.

MOLECULAR MASS
Cell Type Unreduced Reduced
TCRa 45-60 kDa
TCRb 40-50 kDa
TCRg 45-60 kDa
TCRd 40-60 kDa
pTCRa 33 kDa
CD3g 25kDa
CD3d 20 kDa
CD3e 20 kDa
z chain 16 kDa
h chain 22 kDA

POST-TRANSCRIPTIONAL MODIFICATION: No information.

POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD3

The ab heterodimer recognizes peptide antigen bound to MHC antigens.  The affinity of the interaction between the TCR and the MHC/peptide complex is in the range 10-7 M - 10-4 M.  The co-crystal structure of TCR and peptide-MHC reveals that the TCR VDJC junction, which is equivalent to the 3rd complementarity-determining region (CDR3) of antibodies, interacts directly with the peptide and that the CDR1- and CDR2-like regions of the TCR contact peptide and the MHC antigen.  Superantigen binds to non-polymorphic regions of TCRVb . Intracellularly, Fyn is associated with the CD3/TCR complex. Phosphorylated ITAM motifs of the CD3 and z chains bind to SH2 domains of intracellular signaling molecules like phosphorylated z chains which bind to ZAP-70.  The gd TCR appears to recognize peptide and nonpeptide antigens unresticted by the MHC.  The data indicates the same gd TCR also recognizes other antigens restricted by the MHC. 



Function
Recognition of antigen leads to signal transduction mediated by the invariant chains and subsequently T cell activation. Consequences of binding by TCR depend on antigen density and affinity may result in unresponsivenesss.  Signal transduction involves tyrosine kinase and phospholipase C activation followed by phosphoinositide turnover and activation of several second messenger pathways.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD3 IN INTACT ANIMAL: No information.


Comments
Although TCR genes contain fewer variable region segments than antibody genes, the potential repertoire can be argued to be higher than that of antibodies due to the relative abundance of J-region segments and greater flexibility in the joining of variable (V)-, diversity (D)- and joining (J)- segments.  Rearrangement of the TCR genes is similar to that of antibody genes and occurs at the CD4-/CD8- stage of thymic development, but the TCR genes do not undergo somatic mutation after rearrangement.  Selection of the receptor repertoire takes place in the thymic cortex while the thymocytes coexpress CD4 and CD8 and low levels of the TCR.  Mature thymocytes expressing CD4 or CD8 and high levels of the TCR complex then leave the medulla for the periphery.  Mice deficient in components of the CD3/TCR complex are arrested in development of their T cell repertoire.  Diversity in the gd TCR appears to be greater than for the ab TCR and BCR.  Recent reviews provide evidence that shows the genes encoding the immunoglobulin and the TCRs originated early in the course of evolution, between 550 to 450 million years ago (G. W. Litman, M. K. Anderson, and J. P. Rast. Evolution of antigen binding receptors. Annu.Rev.Immunol. 17:109-147, 1999).   Of interest, the studies show that the genes encoding ab and gd TCRs were separate indicating divergence occurred early in the course of vertebrate evolution.

MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD3: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD3: No information.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
Antibodies
2B3C   View Reactivity
8C8   View Reactivity
8E6   View Reactivity
CA17.2A12   View Reactivity
CT-3   View Reactivity
FN-18   View Reactivity
HIT3A   View Reactivity
LT97A   View Reactivity
MM1A   View Reactivity
SP34   View Reactivity
UCHT1   View Reactivity

Revised June 25, 2008


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