Killer cell immunoglobulin-like receptor 2DL1 is a protein that in humans is encoded by the KIR2DL1 gene. KIR2DL1 is an important receptor that is usually found on Natural Killer Cells (NK Cells). This receptor’s job is to send inhibitory signals. This means that the receptor will communicate with a cell and tell it to stop what it is doing when it is not needed. This usually happens when a cell is healthy and does not need NK cells to release toxic proteins to kill that healthy cell. This receptor specifically recognizes HLA-C2 molecules on these healthy cells, which are just proteins that help receptors know they are a healthy cell. KIR2DL1 is important because it helps our immune system stay healthy. Our KIR2DL1 receptors are needed to tell our body and other cells what needs to be killed and what is important to stay because it is healthy for us. Without our KIR2DL1 receptors identifying the bad, the bad cells might start attacking our bodies without the NK cells even knowing they had a job to do. As well as without our KIR2DL1 receptors identifying the good our bodies would just start attacking all the good cells all the time. We need these receptors to make everything else work in this part of our immune system.
Function 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, KIR2DL4, 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. Natural Killer cells, also known as NK cells are cells that listen to a signal and then act on it. They check other cells to see if they say HLA-C2, and if they do then they let them be, although if they don’t they start activating. These natural killer cells have toxic proteins that can kill another cell if released. They will try to break open and kill this cell with their injections of toxic chemicals, which are usually Perforin and Granzymes. Natural Killer cells need inhibitory receptors to help the immune system not attack healthy cells. Healthy cells have MHC-1 molecules on them and the inhibitory receptors will recognize that as a healthy cell and tell the NK cells not to kill them. MHC-1 is a family of antigen presenting molecules. HLA-C2 is a molecule that belongs in that family but works best with NK cells. Inhibitory receptors are needed so that NK cells don't go and kill all the healthy cells. When KIR2DL1 binds to HLA-C2 on a healthy cell, an inhibitory signal will communicate with the natural killer cell and turn off its killing instinct and tell it it's a safe cell. This communication will stop the natural killer cell from releasing toxic chemicals. The toxic chemicals that are usually released at this time will be blocked. The NK cell will completely detach from the healthy cell, leaving it unharmed. This all helps prevent damage to healthy cells and make sure the normal tissues don't get destroyed from the release of NK cell toxic chemicals. In contrast to the KIR2DL1 inhibitory receptors which focus on stopping natural killer cells from killing healthy cells, we also have KIR2DS1 activating receptors. KIR2DS1 activating receptors encourage cells to activate, causing a killing response. The importance of KIR2DS1 is that the killing response allows the body to clean up dead, infected or compromised cells by communicating with the NK cells and encouraging them to destroy these cells. Therefore, the Natural Killer cells attach to a cell and analyze it, weighting out the KIR2DL1 and the KIR2DS1 signals. Depending on the strength of the signals, KIR2DL1 inhibitory receptors begin a biochemical tug of war with the activating KIR2DS1 receptors. Whichever signal is stronger (denser connection with the cell targets) wins and then causes the reaction of the NK Cell. If the inhibitory receptor is stronger the healthy cell will remain alive. However if the activating receptor is stronger that cell will be destroyed from the release of Perforin and Granzymes. Activating receptors will notice when cells do not look healthy, this can come in forms of infection, stress, and damage. First there are stress signals which release certain proteins that are identifiable, these cells are usually damaged by heat or DNA mutations. There are also infected cells that show viral proteins which makes them look like a bad cell. The next one that activating receptors identify right away is antibody tags, which are cells covered in antibodies from the immune system. If inhibitory signals did not exist, natural killer cells would destroy healthy cells that we need in our immune system. If activating signals did not exist, infectious or cancerous cells would not be able to be detected and they would roam around freely harming our immune systems. The body would not be able to detect or kill viruses, or bacteria. If we did not have both of these receptors our immune system would completely fail.
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