CD27 is a member of the

tumor necrosis factor receptor The tumor necrosis factor receptor superfamily (TNFRSF) is a protein superfamily of cytokine receptors characterized by the ability to bind tumor necrosis factors (TNFs) via an extracellular cysteine-rich domain. With the exception of nerve grow ...

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 stimula ...

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 Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT, CD117 (cluster of differentiation 117) or mast/stem cell growth factor receptor (SCFR). Multiple transcript variants encoding diff ...

, medium

Gata2 GATA2 or GATA-binding factor 2 is a transcription factor, i.e. a nuclear protein which regulates the expression of genes. It regulates many genes that are critical for the embryonic development, self-renewal, maintenance, and functionality of bl ...

, 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 chromosome17q23.3. PECAM-1 plays a key role in removing aged neutrop ...

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 very first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within ...

generated in the

aorta-gonad-mesonephros The aorta-gonad-mesonephros (AGM) is a region of embryonic mesoderm that develops during embryonic development from the para-aortic splanchnopleura in chick, mouse and human embryos. The very first adult definitive haematopoietic stem cells, capa ...

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

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells 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 r ...

s as well as

NK cells Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represen ...

and activated

B cell B cells, also known as B lymphocytes, are a type of white blood cell 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 ...

s. It is a type I

transmembrane protein A transmembrane protein (TP) is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequentl ...

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 The tumor necrosis factor receptor superfamily (TNFRSF) is a protein superfamily of cytokine receptors characterized by the ability to bind tumor necrosis factors (TNFs) via an extracellular cysteine-rich domain. With the exception of nerve growth ...

. This receptor is required for generation and long-term maintenance of

T cell immunity Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in ...

. It binds to ligand

CD70 CD70 (Cluster of Differentiation 70) is a protein that in humans is encoded by ''CD70'' gene. CD70 is a ligand for CD27. Clinical significance The CD70 protein is expressed on highly activated lymphocytes (like in T- and B-cell lymphomas). It i ...

, 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 pa ...

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 peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

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 protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...

and MAPK8/

JNK c-Jun N-terminal kinases (JNKs), were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and ar ...

. 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 1980s. Fo ...

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 grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

induced by this receptor. In murine γδ T cells its expression has been correlated with the secretion of

IFNγ Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock ...

Clinical significance

As a drug target

Varlilumab Varlilumab ( INN; development code CDX-1127) is a monoclonal antibody designed for immunotherapy for solid tumors and hematologic malignancies. It is an anti-CD27 antibody and helps activate T-cells. This drug was developed by Celldex Therapeut ...

is an

IgG1 Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG a ...

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 Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with

SIVA1 Apoptosis regulatory protein Siva is a protein that in humans is encoded by the ''SIVA1'' gene. This gene encodes a protein with an important role in the apoptotic (programmed cell death) pathway induced by the CD27 antigen, a member of the tumor ...

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, an ...

and

TRAF3 TNF receptor-associated factor (TRAF3) is a protein that in humans is encoded by the TRAF3 gene. Function The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate wit ...

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