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.
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.
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).
MHC class I polypeptide–related sequence A (MICA) is a highly polymorphic cell surface glycoprotein encoded by the MICA gene located within MHC locus. MICA is related to MHC class I and it has similar domain structure, however, it is not associated with β2-microglobulin nor binds peptides as conventional MHC class I molecules do. MICA rather functions as a stress-induced ligand (as a danger signal) for integral membrane protein receptor NKG2D ("natural-killer group 2, member D"). MICA is broadly recognized by NK cells, γδ T cells, and CD8+ αβ T cells which carry NKG2D receptor on their cell surface and which are activated via this interaction.
Natural cytotoxicity triggering receptor 1 is a protein that in humans is encoded by the NCR1 gene. NCR1 has also been designated as CD335 (cluster of differentiation, NKP46, NKp46, NK-p46, and LY94.
Sialic acid-binding Ig-like lectin 7 is a protein that in humans is encoded by the SIGLEC7 gene. SIGLEC7 has also been designated as CD328.
Killer cell immunoglobulin-like receptor 2DS4 is a protein that in humans is encoded by the KIR2DS4 gene.
NKG2-C type II integral membrane protein or NKG2C is a protein that in humans is encoded by the KLRC2 gene. It is also known as or cluster of differentiation 159c (CD159c).
Natural cytotoxicity triggering receptor 2 is a protein that in humans is encoded by the NCR2 gene. NCR2 has also been designated as CD336, NKp44, NKP44; NK-p44, LY95, and dJ149M18.1.
Hematopoietic cell signal transducer is a protein that in humans is encoded by the HCST gene.
UL16 binding protein 2 (ULBP2) is a cell surface glycoprotein encoded by ULBP2 gene located on the chromosome 6. ULBP2 is related to MHC class I molecules, but its gene maps outside the MHC locus. The domain structure of ULBP2 differs significantly from those of conventional MHC class I molecules. It does not contain the α3 domain and the transmembrane segment. ULBP2 is thus composed of only the α1α2 domain which is linked to the cell membrane by the GPI anchor.
UL16 binding protein 1 (ULBP1) is a cell surface glycoprotein encoded by ULBP1 gene located on the chromosome 6. ULBP1 is related to MHC class I molecules, but its gene maps outside the MHC locus. The domain structure of ULBP1 differs significantly from those of conventional MHC class I molecules. It does not contain the α3 domain and the transmembrane segment. ULBP1 is thus composed of only the α1α2 domain which is linked to the cell membrane by the GPI anchor. It functions as a stress-induced ligand for NKG2D receptor. ULBP1 is, for example, upregulated during HCMV infection. Binding of HCMV-encoded UL16 glycoprotein to ULBP1 interferes with cell surface localization of ULBP1; this represents another mechanism by which HCMV-infected cells might escape the immune system.
C-type lectin domain family 1 member B is a protein that in humans is encoded by the CLEC1B gene.
Leukocyte immunoglobulin-like receptor subfamily A member 2 is a protein that in humans is encoded by the LILRA2 gene.
C-type lectin domain family 2 member D is a protein that in humans is encoded by the CLEC2D gene.
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.
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).
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.
