CD27 is a member of the tumor necrosis factor receptor superfamily. It is currently of interest to immunologists as a co-stimulatory

immune checkpoint Immune checkpoints are regulators of the immune system. These pathways are crucial for self-tolerance, which prevents the immune system from attacking cells indiscriminately. However, some cancers can protect themselves from attack by stimulat ...

molecule, and is the target of an anti-cancer drug in clinical trials.

Expression

During mouse embryonic development, specific (medium) expression levels of CD27 (in addition to high cKit, medium Gata2, and high

CD31 Platelet endothelial cell adhesion molecule (PECAM-1) also known as cluster of differentiation 31 (CD31) is a protein that in humans is encoded by the ''PECAM1'' gene found on chromosome 17, chromosome17q23.3. PECAM-1 plays a key role in removi ...

expression levels) define the very first adult definitive

hematopoietic stem cells Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the ...

generated in the

aorta-gonad-mesonephros The aorta-gonad-mesonephros (AGM) is a region of embryonic germ layer#Mesoderm, mesoderm that develops during embryonic development from the para-aortic splanchnopleura in chick, mouse and human embryos. The very first adult definitive Hæmatopoiet ...

region. Furthermore, CD27 is expressed on both naïve and activated effector

T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

s as well as NK cells and activated

B cell B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...

s. It is a

type I transmembrane protein A single-pass membrane protein also known as single-spanning protein or bitopic protein is a transmembrane protein that spans the lipid bilayer only once. These proteins may constitute up to 50% of all transmembrane proteins, depending on the or ...

with cysteine-rich domains, but once T cells have become activated, a soluble form of CD27 can be shed.

Function

The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor is required for generation and long-term maintenance of T cell immunity. It binds to ligand

CD70 CD70 (Cluster of Differentiation 70) is a protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within or ...

, and plays a key role in regulating B-cell activation and immunoglobulin synthesis. When CD27 binds CD70, a signaling cascade leads to the differentiation and clonal expansion of T cells. The cascade also results in improved survival and memory of

cytotoxic T cell A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular ...

s and increased production of certain

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

s. This receptor transduces signals that lead to the activation of

NF-κB Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a family of transcription factor protein complexes that controls transcription (genetics), transcription of DNA, cytokine production and cell survival. NF-κB is found i ...

and MAPK8/ JNK. Adaptor proteins TRAF2, TRAF3, and TRAF5 have been shown to mediate the signaling process of this receptor via

ubiquitin Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 19 ...

ation. CD27-binding protein ( SIVA), a proapoptotic protein, can bind to this receptor and is thought to play an important role in the

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

induced by this receptor. In murine

γδ T cells Gamma delta T cells (γδ T cells) are T cells that have a γδ T-cell receptor (TCR) on their surface. Most T cells are αβ (alpha beta) T cells with TCR composed of two glycoprotein chains called α (alpha) and β (beta) TCR chains. In contrast, ...

its expression has been correlated with the secretion of IFNγ.

Clinical significance

As a drug target

Varlilumab is an IgG1 antibody that binds to CD27 and is an experimental cancer treatment. This agonist antibody stimulates CD27 when it binds. The drug is in early clinical trials and appears to stimulate T cells and increase production of cytokines such as interferon-gamma.

Interactions

CD27 has been shown to interact with SIVA1,

TRAF2 TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, a ...

and TRAF3.

Mutations

Some mutations can decrease the expression of CD27. Three such mutations, C53Y, C96Y, and R107C, are located in the cysteine-rich domains of CD27.

References

External links

* * {{membrane-protein-stub