NKG2

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killer cell lectin-like receptor subfamily C, member 1
Identifiers
SymbolKLRC1
Alt. symbolsNKG2, NKG2-A, NKG2-B, CD159a
Chr. 12 p13
Search for
StructuresSwiss-model
DomainsInterPro

NKG2 also known as CD159 (Cluster of Differentiation 159) is a receptor for

CD94 to make an inhibitory receptor (CD94/NKG2
).

IPH2201 is a monoclonal antibody targeted at NKG2A.[1]

Gene expression

In both humans and mice, genes encoding the NKG2 family are clustered – in human genome on chromosome 12, in mouse on chromosome 6.[2] They are generally expressed on NK cells and a subset of CD8+ T cells, although the expression of NKG2D was also confirmed on γδ T cells, NKT cells, and even on some subsets of CD4+ T cells or myeloid cells. NKG2D expression can also be present on cancer cells and is proven to stimulate oncogenic bioenergetic metabolism, proliferation and metastases generation.[3]

On NK cells, NKG2 genes are expressed through the ontogeny as well as in adulthood. As about 90% of fetal NK cells express NKG2 genes, one of the proposed functions of the gene family is contribution to self-tolerance.[4] The level of expression of NKG2 genes is not constant, rather it is affected by cytokine environment (mainly interleukin-2 (IL-2), IL-7 and IL-15).[5]

For CD8+ T lymphocytes, NKG2 family expression is believed to be a marker of activated or memory T cells. The expression is triggered namely by IL-15, IL-12, IL-10 and TGF-β. CD94/NKG2 expression is shown to significantly increase the survival of T cells.[4]

Structure

NKG2 are members of the

homodimers.[6]

Inhibitory molecules

DAP-12 or DAP-10, depending on the isoform. There are two isoforms in mice – the long isoform (NKG2D-L) pairs only with DAP-10, whereas the short isoform (NKG2-S) can also pair with DAP-12. Only long isoform is present in humans.[6]

intracellular compartments.[2]

Signalling

Inhibitory NKG2

DAP-12, on the other hand, recruite the Src homology domain containing kinases Syk (spleen tyrosine kinase) or Zap70 (Zeta-chain-associated protein kinase 70). Kinase activation is followed by NK cell degranulation and transcription of cytokine and chemokine genes.[6]

DAP-10 connects to GRB2 or p85, leading to signalling through phosphoinositide 3-kinase (PI3K) and other molecules, leading to cytotoxicity.[6]

Ligands

Ligands of CD94/NKG2 heterodimeric molecules are nonclassical MHC class I molecules – Qa1b molecules in mice and HLA-E in humans. These molecules both present sequences from the digested leading peptides of classical MHC class I molecules. This enables the monitoring of classical MHC class I expression on target cells.[6]

MIC-A) and MIC-B, and also other stress-induced proteins common to humans and mice – retinoic acid early transcript 1 (Rae1) and RAET1 in humans, H60 and UL16-binding protein-like transcript 1 (Mult1) in mice, and the UL16-binding proteins (ULBPs) in humans.[3]

Function

CD94/NKG2

NKG2C and NKG2E (and its splice variant NKG2H) recognize the same ligand with different (usually lower in physiological conditions) affinity. However, the affinity for HLA-E (or Qa1b) can drastically change after a small change in the presented peptide, which can lead to NK cell activation.[4]

LCMV, HSV-1, Influenza and Listeria monocytogenes infections in mice. In cancers, a role of CD94/NKG2 was demonstrated for melanoma, cervical cancer, lymphoma/leukemia and more. NKG2 match can also prevent graft versus leukemia effect (GvL) as well as the graft versus host disease (GvHD).[2]

NKG2D

pathogenicity.[3]

See also

References

External links

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