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 B (MICB) is a protein that is encoded by the MICB gene located within MHC locus. MICB is related to MHC class I and has similar domain structure, which is made up of external α1α2α3 domain, transmembrane segment and C-terminal cytoplasmic tail. MICB is a stress-induced ligand for NKG2D receptor. The heat shock stress pathway is involved in the regulation of MICB expression as transcription of MICB is regulated by promoter heat shock element.
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.
Leukocyte immunoglobulin-like receptor subfamily B member 1 is a protein that in humans is encoded by the LILRB1 gene.
NKG2-F type II integral membrane protein is a protein that in humans is encoded by the KLRC4 gene.
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.
Retinoic acid early transcript 1E(RAET1E) is a cell surface glycoprotein encoded by RAET1E gene located on the chromosome 6. RAET1E is related to MHC class I molecules, but its gene maps outside the MHC locus. RAET1E is composed of external α1α2 domain, transmembrane segment and C-terminal cytoplasmic tail. RAET1E functions as a stress-induced ligand for NKG2D receptor.
Immunoevasins are proteins expressed by some viruses that enable the virus to evade immune recognition by interfering with MHC I complexes in the infected cell, therefore blocking the recognition of viral protein fragments by CD8+ cytotoxic T lymphocytes. Less frequently, MHC II antigen presentation and induced-self molecules may also be targeted. Some viral immunoevasins block peptide entry into the endoplasmic reticulum (ER) by targeting the TAP transporters. Immunoevasins are particularly abundant in viruses that are capable of establishing long-term infections of the host, such as herpesviruses.
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.
Induced-self antigen is a marker of abnormal self, which can be recognized upon infected and transformed cells. Therefore, the recognition of "induced self" is an important strategy for surveillance of infection or tumor transformation - it results in elimination of the affected cells by activated NK cells or other immunological mechanisms. Similarly γδ T cells can recognize induced-self antigens expressed on cells under stress conditions.
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).
Retinoic acid early transcript 1L (RAET1L) is a cell surface glycoprotein encoded by RAET1L gene located on the chromosome 6. RAET1L is related to MHC class I molecules, but its gene maps outside the MHC locus. RAET1L is composed of the α1α2 domain and is linked to the cell membrane by the GPI anchor. It functions as a stress-induced ligand for NKG2D receptor. Its expression is, for example, triggered in course of HCMV infection, but HCMV alters its function. HCMV-encoded UL16 glycoprotein retains ULBP6 inside the cells, preventing it from reaching the cell surface and being exposed to cells of the immune system.
Murine UL16 binding protein-like transcript (MULT-1) is a murine cell surface glycoprotein encoded by MULT-1 gene located on murine chromosome 10. MULT-1 is related to MHC class I and is composed of α1α2 domain, a transmembrane segment, and a large cytoplasmic domain. MULT-1 functions as a stress-induced ligand for NKG2D receptor.
Retinoic acid early inducible 1 (RAE-1) family of murine cell surface glycoproteins is composed of at least five members (RAE-1α-ε). Genes encoding these proteins are located on mouse chromosome 10. RAE-1 proteins are related to MHC class I, they are made up of external α1α2 domain which is linked to the cell membrane by the GPI anchor. They function as stress-induced ligands for NKG2D receptor and their expression is low or absent on normal cells. However, they are constitutively expressed on some tumour cells and they can be upregulated by retinoic acid.
The histocompatibility 60 (H60) was originally identified as a transplant rejection antigen and it is a family of murine cell surface glycoproteins contains three members: H60a, H60b, H60c. The genes encoding these proteins are located on murine chromosome 10. H60 family members are related to MHC class I. H60a and H60b consist of external α1α2 domain, a transmembrane segment, and a cytoplasmic domain. H60c is made up of α1α2 domain which is linked to the cell membrane by GPI anchor. All these proteins function as stress-induced ligands for NKG2D receptor.
