KLRC2

Last updated
KLRC2
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases KLRC2 , CD159c, NKG2-C, NKG2C, killer cell lectin like receptor C2
External IDs OMIM: 602891 HomoloGene: 135919 GeneCards: KLRC2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002260

n/a

RefSeq (protein)

NP_002251

n/a

Location (UCSC) Chr 12: 10.43 – 10.44 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

NKG2-C type II integral membrane protein or NKG2C is a protein that in humans is encoded by the KLRC2 gene. [3] [4] It is also known as or cluster of differentiation 159c (CD159c).

Contents

Function

Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. NK cells preferentially express several calcium-dependent (C-type) lectins, which have been implicated in the regulation of NK cell function. The group, designated KLRC (NKG2) are expressed primarily in natural killer (NK) cells and encodes a family of transmembrane proteins characterized by a type II membrane orientation (extracellular C terminus) and the presence of a C-type lectin domain. The KLRC (NKG2) gene family is located within the NK complex, a region that contains several C-type lectin genes preferentially expressed on NK cells. KLRC2 alternative splice variants have been described but their full-length nature has not been determined. [4]

Interactions

KLRC2 has been shown to interact and form dimers with CD94. [5] [6] The CD94/NKG2C heterodimer can bind to HLA-E [7] [8] and this binding leads to NK cells activation.

During infection with human cytomegalovirus, peptides derived from the virus are presented on HLA-E and natural killer cells that express the CD94/NKG2C receptor can specifically recognise the virus peptides. This recognition leads to activation, expansion, and differentiation of adaptive NK cells. [9]

See also

Related Research Articles

<span class="mw-page-title-main">Natural killer cell</span> Type of cytotoxic lymphocyte

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 represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cell and other intracellular pathogens acting at around 3 days after infection, and respond to tumor formation. Typically, immune cells detect the antigen presented on major histocompatibility complex (MHC) on infected cell surfaces, triggering cytokine release, causing the death of the infected cell by lysis or apoptosis. NK cells are unique, however, as they have the ability to recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of MHC class 1. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.

<span class="mw-page-title-main">HLA-E</span> Protein-coding gene in the species Homo sapiens

HLA class I histocompatibility antigen, alpha chain E (HLA-E) also known as MHC class I antigen E is a protein that in humans is encoded by the HLA-E gene. The human HLA-E is a non-classical MHC class I molecule that is characterized by a limited polymorphism and a lower cell surface expression than its classical paralogues. The functional homolog in mice is called Qa-1b, officially known as H2-T23.

Killer-cell immunoglobulin-like receptors (KIRs), are a family of type I transmembrane glycoproteins expressed on the plasma membrane of natural killer (NK) cells and a minority of T cells. At least 15 genes and 2 pseudogenes encoding KIR map in a 150-kb region of the leukocyte receptor complex (LRC) on human chromosome 19q13.4.

<span class="mw-page-title-main">KLRD1</span>

CD94, also known as killer cell lectin-like receptor subfamily D, member 1 (KLRD1) is a human gene.

NKG2 also known as CD159 is a receptor for natural killer cells. There are 7 NKG2 types: A, B, C, D, E, F and H. NKG2D is an activating receptor on the NK cell surface. NKG2A dimerizes with CD94 to make an inhibitory receptor (CD94/NKG2).

<span class="mw-page-title-main">CD69</span>

CD69 is a human transmembrane C-Type lectin protein encoded by the CD69 gene. It is an early activation marker that is expressed in hematopoietic stem cells, T cells, and many other cell types in the immune system. It is also implicated in T cell differentiation as well as lymphocyte retention in lymphoid organs.

<span class="mw-page-title-main">TYROBP</span> Protein-coding gene in the species Homo sapiens

TYRO protein tyrosine kinase-binding protein is an adapter protein that in humans is encoded by the TYROBP gene.

<span class="mw-page-title-main">CD244</span> Protein found in humans

CD244 also known as 2B4 or SLAMF4 is a protein that in humans is encoded by the CD244 gene.

<span class="mw-page-title-main">KIR2DL1</span> Protein-coding gene in the species Homo sapiens

Killer cell immunoglobulin-like receptor 2DL1 is a protein that in humans is encoded by the KIR2DL1 gene.

<span class="mw-page-title-main">KIR2DL4</span> Protein-coding gene in the species Homo sapiens

Killer cell immunoglobulin-like receptor 2DL4 is a protein that in humans is encoded by the KIR2DL4 gene.

<span class="mw-page-title-main">KLRC4</span> Protein-coding gene in the species Homo sapiens

NKG2-F type II integral membrane protein is a protein that in humans is encoded by the KLRC4 gene.

<span class="mw-page-title-main">KLRB1</span> Protein-coding gene in humans

Killer cell lectin-like receptor subfamily B, member 1, also known as KLRB1, NKR-P1A or CD161, is a human gene.

<span class="mw-page-title-main">KLRG1</span> Protein-coding gene in humans

Killer cell lectin-like receptor subfamily G member 1 is a protein that in humans is encoded by the KLRG1 gene.

<span class="mw-page-title-main">HCST (gene)</span> Protein-coding gene in the species Homo sapiens

Hematopoietic cell signal transducer is a protein that in humans is encoded by the HCST gene.

<span class="mw-page-title-main">CLEC1B</span> Protein-coding gene in humans

C-type lectin domain family 1 member B is a protein that in humans is encoded by the CLEC1B gene.

<span class="mw-page-title-main">Killer activation receptor</span> Class of protein

Killer Activation Receptors (KARs) are receptors expressed on the plasmatic membrane of Natural Killer cells. KARs work together with inhibitory receptors, which inactivate them in order to regulate the NK cells functions on hosted or transformed cells. These two kinds of specific receptors have some morphological features in common, such as being transmembrane proteins. The similarities are specially found in the extracellular domains and, the differences tend to be in the intracellular domains. KARs and KIRs can have tyrosine containing activatory or inhibitory motifs in the intracellular part of the receptor molecule.

<span class="mw-page-title-main">NKG2D</span> Protein-coding gene in the species Homo sapiens

NKG2D is an activating receptor (transmembrane protein) belonging to the NKG2 family of C-type lectin-like receptors. NKG2D is encoded by KLRK1 (killer cell lectin like receptor K1) gene which is located in the NK-gene complex (NKC) situated on chromosome 6 in mice and chromosome 12 in humans. In mice, it is expressed by NK cells, NK1.1+ T cells, γδ T cells, activated CD8+ αβ T cells and activated macrophages. In humans, it is expressed by NK cells, γδ T cells and CD8+ αβ T cells. NKG2D recognizes induced-self proteins from MIC and RAET1/ULBP families which appear on the surface of stressed, malignant transformed, and infected cells.

CD94/NKG2 is a family of C-type lectin receptors which are expressed predominantly on the surface of NK cells and a subset of CD8+ T-lymphocyte. These receptors stimulate or inhibit cytotoxic activity of NK cells, therefore they are divided into activating and inhibitory receptors according to their function. CD94/NKG2 recognize nonclassical MHC glycoproteins class I (HLA-E in human and Qa-1 molecules in the mouse).

<span class="mw-page-title-main">Adaptive NK cell</span> Specialized subtype of cytotoxic lymphocyte

An adaptive natural killer (NK) cell or memory-like NK cell is a specialized natural killer cell that has the potential to form immunological memory. They can be distinguished from cytotoxic NK (cNK) cells by their receptor expression profile and epigenome. Adaptive NK cells are so named for properties which they share with the adaptive immune system. Though adaptive NK cells do not possess antigen specificity, they exhibit dynamic expansions of defined cell subsets, increased proliferation and long-term persistence for up to 3 months in vivo, high IFN-γ production, potent cytotoxic activity upon ex vivo restimulation, and protective memory responses.

<span class="mw-page-title-main">Paired receptors</span>

Paired receptors are pairs or clusters of receptor proteins that bind to extracellular ligands but have opposing activating and inhibitory signaling effects. Traditionally, paired receptors are defined as homologous pairs with similar extracellular domains and different cytoplasmic regions, whose genes are located together in the genome as part of the same gene cluster and which evolved through gene duplication. Homologous paired receptors often, but not always, have a shared ligand in common. More broadly, pairs of receptors have been identified that exhibit paired functional behavior - responding to a shared ligand with opposing intracellular signals - but are not closely homologous or co-located in the genome. Paired receptors are highly expressed in the cells of the immune system, especially natural killer (NK) and myeloid cells, and are involved in immune regulation.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000205809 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. Plougastel B, Trowsdale J (Apr 1998). "Sequence analysis of a 62-kb region overlapping the human KLRC cluster of genes". Genomics. 49 (2): 193–9. doi:10.1006/geno.1997.5197. PMID   9598306.
  4. 1 2 "Entrez Gene: KLRC2 killer cell lectin-like receptor subfamily C, member 2".
  5. Lazetic S, Chang C, Houchins JP, Lanier LL, Phillips JH (Dec 1996). "Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits". Journal of Immunology. 157 (11): 4741–5. PMID   8943374.
  6. Ding Y, Sumitran S, Holgersson J (May 1999). "Direct binding of purified HLA class I antigens by soluble NKG2/CD94 C-type lectins from natural killer cells". Scandinavian Journal of Immunology. 49 (5): 459–65. doi: 10.1046/j.1365-3083.1999.00566.x . PMID   10320637. S2CID   28500838.
  7. Braud VM, Allan DS, O'Callaghan CA, Söderström K, D'Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI, Phillips JH, Lanier LL, McMichael AJ (Feb 1998). "HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C.". Nature. 391 (6669): 795–9. Bibcode:1998Natur.391..795B. doi:10.1038/35869. PMID   9486650. S2CID   4379457.
  8. Lee N, Llano M, Carretero M, Ishitani A, Navarro F, López-Botet M, Geraghty DE (Apr 1998). "HLA-E is a major ligand for the natural killer inhibitory receptor CD94/NKG2A". PNAS. 95 (9): 5199–204. Bibcode:1998PNAS...95.5199L. doi: 10.1073/pnas.95.9.5199 . PMC   20238 . PMID   9560253.
  9. Hammer Q, Rückert T, Borst EM, Dunst J, Haubner A, Durek P, Heinrich F, Gasparoni G, Babic M, Tomic A, Pietra G, Nienen M, Blau IW, Hofmann J, Na IK, Prinz I, Koenecke C, Hemmati P, Babel N, Arnold R, Walter J, Thurley K, Mashreghi MF, Messerle M, Romagnani C (May 2018). "Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells". Nature Immunology. 19 (5): 453–463. doi:10.1038/s41590-018-0082-6. PMID   29632329. S2CID   4718187.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.