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From genes to immunity: How do KIRs determine your immune response?
In the human immune system, natural killer cells (NK cells) play an important role and are responsible for identifying and destroying infected or transformed host cells. The regulation of its function relies on a group of molecules called "killer cell immunoglobulin-like receptors" (KIRs). These membrane proteins not only have a decisive influence on the intensity and duration of immune responses, but also play an important role in the balance between self-tolerance and immune surveillance.
"KIR receptors are able to distinguish MHC I allelic variants, which allows them to efficiently detect virus-infected or transformed cells."
Structure and function of KIR
The KIR gene is located in the leukocyte receptor complex on human chromosome 19 and contains 14 sites covering several disomic genes. KIR receptors can be divided into two categories: stimulatory and inhibitory. In most cases, inhibitory KIR is closely related to self-cell recognition and rejection in previous studies. The presence of these receptors helps avoid attacks on healthy self-cells while allowing the identification and destruction of diseased cells.
For NK cells, KIR receptors are key molecules that directly bind to MHC class I molecules on their surface. Specifically, this effect is achieved through the recognition of MHC class I molecules by inhibitory receptors, which will inhibit the cytotoxic behavior of NK cells. In contrast, when in contact with diseased cells, the inhibitory signal is reduced, which initiates the killing function of NK cells.
KIR receptor diversity and immune response
KIR receptors exhibit a high degree of diversity in the genome, reflecting the selective pressures they have experienced from different pathogens during their evolution. Similar to other components of the immune system, diversity of KIR receptors can improve the overall immune response to viral infections and tumors. Each person's KIR genotype is unique, and the chance of two unrelated individuals having the same KIR genotype is extremely low. This gives our immune system a unique ability to respond to pathogens.
"The great diversity of KIR genotypes gives humans more adaptability to viruses and tumors that they may face in the future."
The association between KIR and disease
Recent research has found that changes in KIR genes may affect a person's susceptibility to certain diseases. In contrast, individuals with dominant inhibitory KIR genotypes may be more susceptible to infection and reproductive failure, but may be more effectively protected against autoimmune diseases. These complex relationships reveal the dual role that KIR plays in the immune system: while protecting the host from foreign pathogens, it must also guard against the risk of autoimmunity.
Stimulatory receptors such as KIR2DS1 and KIR2DS2 have been linked to a variety of autoimmune diseases, further suggesting that increased immune affinity may lead to attack of one's own cells in many cases. At the same time, the presence of KIR3DS1 was found to be associated with the inhibition of the progression of certain cancers, showing the versatility of KIR genotypes in infectious diseases and cancer.
Directions for future research
With the deepening understanding of the function of KIR receptors, the scientific community regards them as potential therapeutic targets. Currently, research on KIR and CAR T cell therapy is gradually underway, aiming to use KIR to enhance the anti-tumor response ability of NK cells. Whether research in this direction can usher in a new era of immunotherapy depends on our understanding and mastery of the mechanisms behind KIR.
So are we ready to use advances in genetic technology to boost our immune systems so they can play a greater role in protecting our health?
