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KIR diversity: Why are the genotypes of different industries so unique?
Killer-cell immunoglobulin-like receptors (KIRs) are a group of transmembrane glycoproteins expressed on natural killer cells (NK cells) and a few T cells. These receptors play a crucial role in regulating the immune system, particularly in distinguishing healthy from diseased cells. The diversity of KIRs is not only a reflection of their genetic makeup, but also of our understanding of the roles they play in immune protection.
KIR receptors are able to recognize MHC I allelic variants, enabling them to detect virus-infected or transformed cells.
In humans, the genes for KIR are encoded by the immune receptor complex (LRC) at a specific location on chromosome 19. This KIR region is approximately 150 kilobases long and contains 14 gene loci, including 7 protein-coding genes and 2 pseudogenes. This high diversity means that approximately 2% of unrelated individuals share the same KIR genotype.
The diversity of KIRs reflects the pressure that rapidly evolving viruses place on the human immune system.
The functions of KIR receptors can be divided into inhibitory and activating. Most KIRs are inhibitory, which inhibit NK cell cytotoxicity after recognizing self-MHC molecules; while activating receptors promote NK cell activation after recognizing variant or non-self antigens. During NK cell development, there is an "education process" that changes KIR expression to maximize the balance between defense and self-tolerance.
The diversity and complexity of these receptors are critical to the role of NK cells in recognizing different cell types. The decision-making process of NK cells depends on the combination of receptors they express. As a result, different individuals may respond very differently to the same immune environment, making the study of KIR applications extremely important across multiple industries.
The role of KIR in the immune system is not limited to protection against viral infections, but also involves susceptibility to autoimmune diseases and cancer.
As contemporary research continues to deepen, we have discovered that the diversity of KIR receptors is closely related to human epidemiology. Certain groups may show different vulnerabilities or protections against different diseases due to their genotype. For example, a genotype with a predominance of inhibitory KIRs may make an individual more susceptible to viral infections but, in some cases, reduce the risk of autoimmune disease.
On the other hand, genotypes with activated KIR may enhance the ability to kill viruses and tumors, but may also increase the risk of autoimmune diseases. Such properties require further research to understand the mechanisms behind them and how this knowledge can be used in the clinic to improve patient treatment.Many recent studies have explored ways to exploit KIR as an alternative activation modality in CAR T-cell therapy.
As cell therapy in cancer treatment becomes a hot topic, the potential of KIR is also widely recognized. By incorporating KIR into CAR T-cell technology, scientists hope to improve the targeting and destructive power of the therapy on cancer cells.
The performance of KIR in the test may bring new opportunities for the treatment of unsolved cancers, but further clinical data is still needed to prove its safety and effectiveness.
Advances in technology and our increased understanding of KIR diversity will allow us to better harness these immune receptors and improve the treatment of many diseases. Will KIR change our future immune strategies and disease predictions in different cultural, geographic and genetic contexts?
