Killer inhibitor receptor

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. They regulate the killing function of these cells by interacting with major histocompatibility (MHC) class I molecules, which are expressed on all nucleated cell types. KIR receptors can distinguish between major histocompatibility (MHC) class I allelic variants, which allows them to detect virally infected cells or transformed cells. Most KIRs are inhibitory, meaning that their recognition of MHC molecules suppresses the cytotoxic activity of their NK cell. Only a limited number of KIRs are activating, meaning that their recognition of MHC molecules activates the cytotoxic activity of their cell. Initial expression of KIRs on NK cells is stochastic, but there is an educational process that NK cells undergo as they mature that alters the expression of KIRs to maximize the balance between effective defense and self-tolerance. As a result of KIR's role in killing unhealthy self-cells and not killing healthy self-cells, KIRs are involved in protection against and propensity to viral infection, autoimmune disease, and cancer. KIR molecules are highly polymorphic, meaning that their gene sequences differ greatly between individuals, and polygenic so that it is extremely rare for two unrelated individuals to possess the same KIR genotype.

Natural killer (NK) cells are a type of lymphocyte cell involved in the innate immune system’s response to viral infection and tumor transformation of host cells. Like T cells, NK cells have many qualities characteristic of the adaptive immune system, including the production of “memory” cells that persist following encounter with antigens and the ability to create a secondary recall response. Unlike T cells, NK cell receptors are germline encoded, and therefore do not require somatic gene rearrangements. Because NK cells target self cells, they have an intricate mechanism by which they differentiate self and non-self cells in order to minimize the destruction of healthy cells and maximize the destruction of unhealthy cells.

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