CD275 ICOSLG (inducible T-cell co-stimulator ligand), ICOS-L, B7-H2 (B7-homologue 2), B7RP-1 (B7-related protein), LICOS (ligand for ICOS)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Dendritic Cell
Monocyte
T Cell
B Cell
Macrophage
Bone Marrow
Leukocyte
Brain
Lung
Kidney
Liver
Pancreas
Thymus
Skeletal muscle
Tonsil
Spleen
Ovary
Placenta
Prostate
Lymph Node
Endothelial Cell
Colon
Testis
Peripheral blood
40 / 40
60 / 60

Expression
CD275 is expressed on endothelial cells, macrophages, dendritic cells, T and B cells and activated monocytes.  Isoform 1 is widely expressed in brain, kidney, liver, lung, pancreas, placenta, skeletal muscle, bone marrow, colon, ovary, prostate, testis, lymph nodes, leukocytes, spleen, thymus and tonsil.  Isoform 2 is detected only in lymph nodes, leukocytes and spleen.  Constitutive expression is further enhanced by treatment with TNF-α in peripheral blood B cells and monocytes, while it is decreased in dendritic cells.

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

CD275 is a single-pass type-1 302 aa glycoprotein.  It contains a transmembrane domain which contains an Ig-like C2-type domain, an 1 Ig-like V-type domain and 5 conserved cysteine residues, a transmembrane domain and a cytoplasmic domain.  CD275 is a member of B7 family of co-stimulatory molecules.

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms.  The isoforms differ at the C-terminal end of the cytoplasmic domain.

POST-TRANSLATIONAL MODIFICATION: No information. 

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD275

CD275 is a T cell co-stimulator ligand for the T cell specific cell surface receptor CD278 (ICOS).

Function
CD275 binds only CD278 and does not bind the other ICOS homologues CD28 or CD152 (CTLA-4).  Engagement of CD278 on activated T cells by CD275 bearing cells increases cytokine secretion, acts as a costimulatory signal for T cell proliferation and also induces B cell proliferation and differentiation into plasma cells. 


   It could play a role in mediating local tissue responses to inflammatory conditions, as well as in modulating the secondary immune response by co-stimulating memory T cell function.  This co-stimulation of anti-CD3-stimulated T cells is reported to promote proliferation and cytokine production. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD275 IN INTACT ANIMAL

CD275 knockout mice have not been described.  Transgenic mice over-expressed with soluble CD275 fusion protein showed lymphoid hyerplasia.  The CD278/CD275 interaction appears to be important in the cognate interaction between T cells and antigen presenting cells and play a role pathological situations such as graft rejection and allergic airway inflammation and  the pathway is a target for therapeutic intervention.  Most studies have focused on signal transduction through CD278 to the T-cell, but by analogy with the other B7 family members, it is possible that signals are transmitted through CD275 to the antigen presenting cell, endothelial or B cell.                            

Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD275: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD275: No information.

ADDITIONAL INSIGHTS

For further information see Yoshinaga, S. K. et al (2000) Int. Immunol. 12: 1439-1447.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene23308O75144
Antibodies

Revised June 25, 2008


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