CD276 

B7-H3 (long) (B7 homolog 3), 4Ig-B7-H3

Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Monocyte
Dendritic Cell
T Cell
Epithelial Cell
Placenta
B Cell
Trophoblast
Heart
Liver
Prostate
Pancreas
Small intestine
Colon
Uterus
Testis
Tumor Cell
NK Cell
40 / 40
110 / 110

Expression
CD276 is expressed on epithelial cells, NK cells activated monocytes, B and T cells and dendritic cell subsets.  Expression is ubiquitous but not detectable in peripheral blood lymphocytes or granulocytes.  Expression is weak in resting monocytes.  There is expression in dendritic cells derived from monocytes and in epithelial cells of sinonasal tissue.  Expression is in extravillous trophoblast cells and Hofbauer cells of the first trimester and term placenta.  Expression is high in heart, liver, placenta, prostate, testis, uterus, pancreas, small intestine, colon and lymphoid organs but there is lower expression in brain, skeletal muscle, kidney, and lung.  Expression was detected in most tumor cell lines tested.

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

CD276 is a single-pass type-1 glycoprotein which has 2 isoforms.  The major isoform, a 508 aa long form, which contains a 26 aa short leader sequence, a 435 aa extracellular domain which contains 2 Ig-like C2-type and 2 Ig-like V-type domains, a 31 aa transmembrane domain and a 42 aa cytoplasmic domain.  The short isoform contains an extracellular domain with only 1 Ig-like C2-type and 1 Ig-like V-type domain, a transmembrane domain and a cytoplasmic domain.  CD276 shares 20-27% amino acid identity with other B7 family members within the Ig gene superfamily.

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 4 different isoforms.

POST-TRANSLATIONAL MODIFICATION: No information.


Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD276: No information.

Function
CD276 is a member of the B7 family of co-stimulatory molecules and is a coinhibitory ligand.  Costimulatory B7 molecules CD80 (B7-1) signal though CD28, CD152 (CTLA-4), CD278 (ICOS) and CD279 (PD-1).  Contradictory results have made the claim of costimulatory functions controversial and most studies indicate CD276 acts as an inhibitor of T cell function.  CD276 proliferates both CD4+ and CD8+ T cells, enhances the induction of cytotoxic T cells and selectively stimulates IFN-γ production in the presence of T cell receptor signaling. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD276 IN INTACT ANIMAL

CD276 may be involved in the development of acute and chronic transplant rejection and in the regulation of lymphocytic activity at the mucosal surfaces.  Studies with CD276 null mice provide evidence of inhibitory functions as these mice develop more severe airway inflammation under Th1-polarizing conditions and develop EAE earlier than wild-type mice.  Furthermore, antigen presenting cells isolated from CD276 null mice show a two-fold increase in alloreactive T-cell proliferation in a MLR response.  Possibly CD276 plays a role in providing the placenta and fetus with a suitable immunological environment throughout pregnancy.  It may play a protective role against NK cell mediated killing.  MAb mediated masking of CD276 resulted in enhanced lysis by NK cells.  Anti-CD276 antibody may be a useful tool for detecting neuroblastoma cells in bone marrow, which is the primary site of neuroblastoma relapse.  
  


Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION IN CD276: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD276: No information.

ADDITIONAL INSIGHTS

For further information see Chapoval, A. I. et al (2001) Nat. Immunol. 2: 269-274.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene80381Q5ZPR3
Antibodies

Revised June 25, 2008


Contact us: Webmaster |  509-335-9515 | Accessibility | Copyright | Policies
College of Veterinary Medicine Washington State University, Pullman, WA, 99164-7010 USA
Copyright 1995-2003 Washington State University