CD278 ICOS (inducible T-cell co-stimulator)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
T Cell
Thymocyte
Th2 Cell
B Cell
55 / 55

Expression
CD278 is expressed on Th2 cells and thymocyte subsets.  Expression is on activated T cells and is seen on the cell surface 12-48 hrs after the activation.  In humans, CD278 is expressed in the thymic medulla of fetal and newborn thymus and in the T-cell zones of lymph nodes.  There is high expression on tonsillar T cells which are closely associated with B cells in the apical light zone of germinal centers, the site of terminal B cell maturation.  Expression is at lower levels in thymus, lung in T cell zones and peripheral blood leukocytes.

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

CD278 is a single-pass type-1 199 aa transmembrane glycoprotein.  It contains an extracellular domain which contains 1 Ig-like V-type domain stablized by conserved cysteine residues and 3 potential N-glycoslation sites, a 23 aa transmembrane domain and a 35 aa cytoplasmic domain.  CD278 belongs to CD28 and CD152 (CTLA-4), a cell-surface receptor family.  These receptors are important regulators of the immune system.  CD28 enhances T cell function essential for an effective antigen-specific immune response, and CD152 counterbalances the CD28-mediated signals and thus prevents an fatal overstimulation of the lymphoid system.  The CD278 amino acid sequence shares 24% and 17% identity, respectively, with CD28 and CD152. 

MOLECULAR MASS

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yeilds 2 different isoforms.

POST-TRANSLATIONAL MODIFICATION

CD278 is N-glycosylated.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD278

Unlike CD28 and CD152, CD278 does not bind CD80 and CD86.  It provides costimulation to memory T cells by interacting with a different B7 family member CD275 (ICOSL).

Function
CD278 forms homodimers and plays a important role in cell-cell signaling, immune response and regulation of cell proliferation.  Expression on activated T cells, plays a critical role in costimulating T cell activation, development, proliferation and cytokine synthesis and cognate interaction with B cells.  There is an enhancement of all basic T cell responses to a foreign antigen namely proliferation, secretion of lymphokines, up-regulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B cells.  CD278 is essential both for efficient interaction between T and B cells and for normal antibody responses to T-cell dependent antigens.  Engagement of CD278 induces secretion of IL-4, IL-5, IL-6, IFN-γ, TNFα and GM-CSF but not IL-2.  The engagement also induces IL-10 secretion and protects pre-activated T cells from apoptosis.  Knockout mice are generally healthy and have normal T cell development and numbers, but the T cells show defective T cell activation and effector function.  CD278 -/- T cells do not make IL-4 and IL-13, resulting in defective Ig switching.  These mice also show impaired germinal center formation. CD278 plays a critical role in CD40-mediated class switching of immunoglobulin isotypes and CD278 is another major regulator of the adaptive immune system. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD278 IN INTACT ANIMAL

Defects in CD278 are the cause of ICOS deficiency which is a form of common variable immunodeficiency (CVID) characterized by recurrent bacterial infections of the repiratory and digestive tracts characteristic of humoral immunodeficiency.  Blockade of CD278 significantly reduced allergic airway disease.  The restricted expression of CD278 on activated cells, together with its role in allergic airway inflammation, EAE and allograft rejection suggests ICOS as a target for immunotherapy.  Anti-CD278 antibody delays graft rejection, apparently by suppressing T cell activation.


Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD278: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD278: No information.

ADDITIONAL INSIGHTS

For further information see Hutloff, A. et al (1999) Nature 397: 263-266.



Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene29851Q9Y6W8
Antibodies

Revised June 25, 2008


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