CD27
Lua error in Module:Infobox_gene at line 53: attempt to index field 'wikibase' (a nil value). CD27 is a member of the tumor necrosis factor receptor superfamily.[1] It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule, and is the target of an anti-cancer drug in clinical trials.[2]
Expression
[edit | edit source]During mouse embryonic development, specific (medium) expression levels of CD27 (in addition to high cKit,[3][4] medium Gata2,[5][6][4] and high CD31[4] expression levels) define the very first adult definitive hematopoietic stem cells generated in the aorta-gonad-mesonephros region.[4] Furthermore, CD27 is expressed on both naïve and activated effector T cells as well as NK cells and activated B cells.[1] It is a type I transmembrane protein with cysteine-rich domains, but once T cells have become activated, a soluble form of CD27 can be shed.[1][2]
Function
[edit | edit source]The protein encoded by this gene is a member of the TNF-receptor superfamily.[7] This receptor is required for generation and long-term maintenance of T cell immunity. It binds to ligand CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis.[1]
When CD27 binds CD70, a signaling cascade leads to the differentiation and clonal expansion of T cells.[7] The cascade also results in improved survival and memory of cytotoxic T cells and increased production of certain cytokines.[8] This receptor transduces signals that lead to the activation of NF-κB and MAPK8/JNK.[7] Adaptor proteins TRAF2, TRAF3, and TRAF5 have been shown to mediate the signaling process of this receptor via ubiquitination.[1][2] CD27-binding protein (SIVA), a proapoptotic protein, can bind to this receptor and is thought to play an important role in the apoptosis induced by this receptor.[9]
In murine γδ T cells its expression has been correlated with the secretion of IFNγ.[10]
Clinical significance
[edit | edit source]As a drug target
[edit | edit source]Varlilumab is an IgG1 antibody that binds to CD27 and is an experimental cancer treatment.[2] This agonist antibody stimulates CD27 when it binds.[2] The drug is in early clinical trials and appears to stimulate T cells and increase production of cytokines such as interferon-gamma.[2][7]
Interactions
[edit | edit source]CD27 has been shown to interact with SIVA1,[11] TRAF2[12][13] and TRAF3.[12][13]
Mutations
[edit | edit source]Some mutations can decrease the expression of CD27. Three such mutations, C53Y, C96Y, and R107C, are located in the cysteine-rich domains of CD27.[1]
References
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Further reading
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External links
[edit | edit source]- CD27+Antigens at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Human CD27 genome location and CD27 gene details page in the UCSC Genome Browser.
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