Language
Country/Area
No result found
The Mystery of KIR Receptors: How Do Natural Killer Cells Distinguish Self from Not-Self?
Natural killer (NK) cells play an important role in the human immune system, especially in resisting viral infections and monitoring cancer cells. Among them, the presence of KIR (killer cell immunoglobulin-like receptor) receptors enables these cells to accurately distinguish between self and non-self, thereby achieving effective attacks on abnormal cells. These receptors not only recognize the state of the cell, but also protect healthy self cells from damage during an attack.
The function of natural killer cells lies in their ability to recognize MHC class I molecules through KIR receptors, ranging from viral infections to cancer-transformed cells.
KIR receptors are responsible for regulating the cytotoxic activity of NK cells, and their working principle mainly depends on their interaction with major histocompatibility complex (MHC) class I molecules. KIR receptors exist in a dual form on the surface of NK cells, some of which have activating functions and others have inhibitory effects. Most KIR receptors are inhibitory and can suppress the cytotoxic activity of NK cells by recognizing MHC molecules. This mechanism ensures the survival of healthy self cells.
In addition, KIR receptor expression is stochastic, but as NK cells mature, they undergo a learning process that allows KIR expression to be adjusted to maximize the balance between defense and self-tolerance. . Such adjustments enable NK cells to effectively attack pathological self cells while keeping healthy cells safe, thereby participating in the protection against viral infections, autoimmune diseases and cancer.
The diversity of KIR receptors and their variation in different individuals allows the human immune response to quickly adapt to viruses or pathogens that emerge during evolution.
These receptors are characterized by classical genetic diversity, with the diversity of KIR genes being exhibited by their location within the leukocyte receptor complex on human chromosome 19. The coding sequences of KIR genes vary greatly between different individuals. Therefore, in most cases, the probability that two unrelated individuals have the same KIR genotype is very small. This diversity suggests that KIR receptors are important for evolving to combat rapidly mutating viruses.
KIR receptors are functionally divided into two types: inhibitory and activating. Inhibitory receptors can regulate NK cell function by recognizing the expression of self-MHC class I molecules, while activating receptors can promote the cytotoxic activity of NK cells by recognizing antigens characteristic of infected or transformed cells. The balance between these two types of receptors is crucial to the effectiveness of NK cells, giving NK cells good cell recognition capabilities and rapid response speed.
The "missing self" hypothesis explains how selective attack between normal tissue and diseased cells is achieved.
Many studies have shown that the expression of KIR receptors is not only determined by genetic factors but also affected by epigenetic mechanisms. This means that while an individual's combination of KIR genes is genetically fixed, environmental factors and other regulatory mechanisms can influence how active KIRs are. Furthermore, KIRs have been shown to be expressed on adult NK cells in fetal liver, revealing the importance of KIR receptors in development.
While our understanding of KIR receptors continues to expand, their role in immune defense and self-tolerance is clearly complex. Different KIR genotypes correspond to different immune responses, allowing these cells to effectively coordinate their operations when facing various pathogens and healthy cells. As more research continues, we will gain a deeper understanding of how these receptors cleverly control the fate of cells while protecting health.
What undiscovered secrets are hidden in the interaction between KIR receptors and NK cells? Will it become a research hotspot in immunology in the future?
