Human natural Killer cell. Image credit: National Institute of Allergy and Infectious Disease via Unsplash.
Immune cells help to protect the body from infections and cancer. One way that they do this is by recognising and destroying harmful cells. Natural killer cells (known as NK cells) can tell whether cells are healthy or harmful based on the molecules that are present on their surface. For example, molecules known as MHC Class I are commonly found on healthy cells whereas cancer cells and those infected with viruses can lose these molecules from their surface.
NK cells use inhibitory receptors to recognise MHC Class I molecules. If they do not detect this molecule on the surface of a cell, the NK cell can become activated and kill the unhealthy cell. In mice, a group of receptors known as the Ly49 family are thought to be responsible for this process. However, Ly49 receptors are complex and their individual roles in NK cells remained unclear.
To investigate, Piersma et al. developed mice without any of the Ly49 receptors. A single receptor was then re-introduced to identify its individual role. These experiments showed that the Ly49 receptor family is required for NK cells to detect a lack of MHC Class I molecules on cells. The receptors also allow NK cells to express certain receptors and to be fully functional. Introducing an individual Ly49 receptor was sufficient to restore these abilities, suggesting that a single receptor can mediate these processes.
The findings of Piersma et al. provide a deeper understanding of how NK cell inhibitory receptors work in mice. Further investigation of the equivalent receptors in humans may aid understanding of the mechanisms involved in recognising harmful changes to cells. In the future, this information may help to improve cancer and anti-viral treatments.
