CD274 B7-H, PDCD1LG1 (programmed cell death 1 ligand 1),  PD-L1
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
T Cell
Dendritic Cell
Monocyte
B Cell
NK Cell
Macrophage
Epithelial Cell
Keratinocyte
Heart
Skeletal muscle
Lung
Placenta
Carcinoma Cell
Lymphoma Cell
40 / 40

Expression
CD274 is expressed on macrophages, epithelial and dendritic cells, NK cells, activated monocytes and activated T- and B-cells.   Upregulation occurs in B cells activated by surface Ig cross-linking.  Upregulation occurs in keratinocytes after LPS and IFN-γ activation.  Expression is high in the heart, skeletal muscle, placenta and lung and weakly in the thymus, spleen, kidney and liver.  There is no expression in brain, colon and small intestine.  Expression is in many tumors including T-cell lymphomas, carcinomas, melanomas and glioblastomas.

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

CD274 is a single-pass type-1 272 aa transmembrane glycoprotein.  It contains an 18 aa signal sequence, a 220 aa extracellular domain which contains a N-terminal Ig-like C2-type domain, an Ig-like V-type domain and has 4 potential N-linked glycosylation sites, a 21 aa transmembrane domain and a 31 aa intracellular cytoplasmic domain.  CD274 is a member of the B7 family of co-stimulatory molecules within the Ig gene superfamily. 

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 3 different isoforms, a full length isoform and 2 shorter isoforms.  
CD274 is found on the plasma membrane (isoform 1).  Isoform 2 has 176 residue and lacks 17-130 aa and isoform 3 consists of 178 aa and lacks residues 179-290.

POST-TRANSLATIONAL MODIFICATION: No information.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD274

CD274 binds CD279 (PD1).

Function
CD274 can act as both a costimulatory and coinhibitory molecule for T cells.  Many studies have provided evidence for CD274 having an inhibitory role in regulating T-cell-mediated immune responses, which is similar to the consequences of CD273 binding to CD279 (PD-1).  CD274 is essential for T cell  proliferation and production of IL-10 and IFN-γ in an IL-2-dependent and a CD274-independent manner.  CD274 is the putative ligand for CD279.  CD274/CD279 signaling appears to be important in the maintenance of peripheral tolerance and in the prevention of tumor rejection  and to inhibit TCR-mediated proliferation and cytokine secretion.  Pathogens may exploit CD274 to evade an immune response.  For example the upregulation of CD274 expression by Shistosoma mansoni induces T cell anergy.  Several studies have demonstrated CD274-mediated costimulation of T cells can
occur in the absence of CD279 suggests the existence of alternative receptors.  CD274 is essential for T cell  proliferation and production of IL-10 and IFN-γ in an IL-2-dependent and a CD274-independent manner. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD274 IN INTACT ANIMAL

Blockade of CD274 may be a useful tool in cancer immunotherapy.


Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD274: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD274: No information.

ADDITIONAL INSIGHTS

For further information see Freeman, G. J. et al (2000) J. Exp. Med. 192: 1027-1034.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene29126Q9NZQ7
Antibodies

Revised June 25, 2008


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