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.
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.
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.
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).
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.
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.
UL16 binding protein 3 (ULBP3) is a cell surface glycoprotein encoded by ULBP3 gene located on the chromosome 6. ULBP3 is related to MHC class I molecules, but its gene maps outside the MHC locus. The domain structure of ULBP3 differs significantly from those of conventional MHC class I molecules. It does not contain the α3 domain and the transmembrane segment. ULBP3 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.
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 1G (RAET1G) is a cell surface glycoprotein encoded by RAET1G gene located on the chromosome 6. RAET1G is related to MHC class I molecules, but its gene maps outside the MHC locus. RAET1G is composed of external α1α2 domain, transmembrane segment and C-terminal cytoplasmic tail. RAET1E functions as a stress-induced ligand for NKG2D receptor.
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.
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.
