Killer cell immunoglobulin-like receptor 3DL2 is a protein that in humans is encoded by the KIR3DL2 gene. [5] [6] [7] The protein IGSF8 (Immunoglobulin superfamily member 8) has been identified as a binding partner of the KIR3DL2 receptor. [8] Binding of IGSF8 to KIR3DL2 expressed on the surface of natural killer (NK) cells acts as an immune checkpoint that inhibits cytotoxic activity and cell killing by NK cells. [8] KIR3DL2 is highly expressed on both NK cells and γδ T cells (a subtype of non-MHC-I restricted T cells). [8]
Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several "framework" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response. This gene is one of the "framework" loci that is present on all haplotypes. [7]
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. In humans, they are encoded in the leukocyte receptor complex (LRC) on chromosome 19q13.4; the KIR region is approximately 150 kilobases and contains 14 loci, including 7 protein-coding genes and 2 pseudogenes.
Leukocyte immunoglobulin-like receptor subfamily B member 1 is a protein that in humans is encoded by the LILRB1 gene.
HLA class I histocompatibility antigen, alpha chain F is a protein that in humans is encoded by the HLA-F gene. It is an empty intracellular molecule that encodes a non-classical heavy chain anchored to the membrane and forming a heterodimer with a β-2 microglobulin light chain. It belongs to the HLA class I heavy chain paralogues that separate from most of the HLA heavy chains. HLA-F is localized in the endoplasmic reticulum and Golgi apparatus, and is also unique in the sense that it exhibits few polymorphisms in the human population relative to the other HLA genes; however, there have been found different isoforms from numerous transcript variants found for the HLA-F gene. Its pathways include IFN-gamma signaling and CDK-mediated phosphorylation and removal of the Saccharomycescerevisiae Cdc6 protein, which is crucial for functional DNA replication.
Killer cell immunoglobulin-like receptor 3DL1 is a protein that in humans is encoded by the KIR3DL1 gene.
Killer cell immunoglobulin-like receptor 2DL1 is a protein that in humans is encoded by the KIR2DL1 gene.
Killer cell immunoglobulin-like receptor 2DL4 is a protein that in humans is encoded by the KIR2DL4 gene.
Leukocyte-associated immunoglobulin-like receptor 1 is a protein that in humans is encoded by the LAIR1 gene. LAIR1 has also been designated as CD305.
Leukocyte immunoglobulin-like receptor subfamily B member 2 is a protein that in humans is encoded by the LILRB2 gene.
Leukocyte immunoglobulin-like receptor subfamily B member 4 is a protein that in humans is encoded by the LILRB4 gene.
SLAM family member 6 is a protein that in humans is encoded by the SLAMF6 gene.
Killer cell immunoglobulin-like receptor 2DS4 is a protein that in humans is encoded by the KIR2DS4 gene.
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.
Leukocyte immunoglobulin-like receptor subfamily B member 3 is a protein that in humans is encoded by the LILRB3 gene.
Immunoglobulin superfamily member 8 is a protein that in humans is encoded by the IGSF8 gene. IGSF8 has also been designated as CD316. IGSF8 is an innate immune checkpoint that inhibits the cytotoxic activity of natural killer (NK) cells. IGSF8 acts by binding to the Killer Ig-like Receptor KIR3DL2. IGSF8 is frequently overexpressed relative to normal tissues in many cancers, included melanoma, urothelial carcinoma, and breast cancer, and has been proposed as a potential therapeutic target in gliomas. In normal tissues, IGSF8 is highly expressed in the brain, where it may contribute to the immune privilege of the central nervous system.
Leukocyte immunoglobulin-like receptor subfamily A member 3 (LILR-A3) also known as CD85 antigen-like family member E (CD85e), immunoglobulin-like transcript 6 (ILT-6), and leukocyte immunoglobulin-like receptor 4 (LIR-4) is a protein that in humans is encoded by the LILRA3 gene located within the leukocyte receptor complex on chromosome 19q13.4. Unlike many of its family, LILRA3 lacks a transmembrane domain. The function of LILRA3 is currently unknown; however, it is highly homologous to other LILR genes, and can bind human leukocyte antigen (HLA) class I. Therefore, if secreted, the LILRA3 might impair interactions of membrane-bound LILRs with their HLA ligands, thus modulating immune reactions and influencing susceptibility to disease.
Leukocyte immunoglobulin-like receptor subfamily A member 2 is a protein that in humans is encoded by the LILRA2 gene.
Killer cell immunoglobulin-like receptor 3DL3 is a protein that in humans is encoded by the KIR3DL3 gene.
Killer cell immunoglobulin-like receptor, two domains, short cytoplasmic tail, 1 is a protein that in humans is encoded by the KIR2DS1 gene.
KIR2DL3, Killer cell immunoglobulin-like receptor 2DL3 is a transmembrane glycoprotein expressed by the natural killer cells and the subsets of the T cells. The KIR genes are polymorphic, which means that they have many different alleles. The KIR genes are also extremely homologous, which means that they are similar in position, structure and evolutionary origin, but not necessarily in function.
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.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.