An Overview of NK Cell Surface Markers

Natural killer (NK) cells are lymphocytes of the innate immune system and play an important role in preventing viral infection and inhibiting cancer development. NK cells account for 10%-15% of the total number of human peripheral blood lymphocytes. Because they express dense cytolytic granules in the cells, they are called large granular lymphocytes. When encountering certain abnormal tumor cells or virus-infected cells, NK cells will be activated spontaneously and release the granule contents-perforin and granzyme-to the target cells. Perforin and granzymes can induce apoptosis in target cells. NK cells need to recognize and adhere to abnormal cells one-to-one to exert cytotoxicity. Therefore, NK cells are considered to be particularly important for the elimination of single-cell tumors, especially leukemias, lymphomas, and metastatic tumor cells. Although NK cells were originally named for their ability to produce cytotoxic effects, NK cells can also produce many cytokines and chemokines, especially interferon-γ (interferon, IFN), tumor necrosis factor (tumor necrosis factor, TNF) α and GM-CSF. In addition to acting directly on tumor cells and virus-infected cells, these cytokines can also promote the differentiation, activation and/or recruitment of other immune cells.

Surface Markers of NK Cell

NK cells develop from common lymphoid progenitor cells (CLP) in the bone marrow. Here, they go through different developmental stages, including NK cell precursors, as well as immature and mature NK cells. Recent findings suggest that development can also occur in secondary lymphoid tissues such as lymph nodes and spleen. During this time, cells are marked for MHC-I (major histocompatibility complex) recognition to avoid targeting healthy, normal cells.

The surface markers expressed on NK cells are numerous and diverse and can be divided into two major groups: human cell surface markers and mouse cell surface markers. Among the human markers, CD16, CD56, CD57, and KIR are particularly noteworthy. These markers are of paramount importance in the classification and identification of NK cells. By understanding these markers and their associated pathways, scientists can gain a deeper appreciation of the remarkable capacities of NK cells and their role in defending the body against harmful pathogens and diseases. The following are some common human NK cell surface markers.

Similarly, mouse cell surface markers such as NK1.1, Ly49, and CD49b have been extensively studied to gain a better understanding of the properties and functions of NK cells in mouse models. These markers have proved invaluable in identifying and characterizing different subsets of NK cells in mice and have been used to dissect the mechanisms underlying their development, activation, and effector functions. The following are some common mouse NK cell surface markers.

NK Cell Activation Markers

The activation of Natural Killer (NK) cells is a critical aspect of their effector function in the immune response. Activated NK cells are characterized by the expression of specific markers that can be used to track their activation and function.

One of the most prominent activation markers of NK cells is CD69, which is expressed on the cell surface following activation. CD69 is involved in the regulation of cytokine production and cytotoxicity, and its expression is an indicator of NK cell activation.

Other activation markers commonly used to identify activated NK cells include CD25, CD137, and CD107a. CD25, also known as interleukin-2 receptor alpha chain, is expressed on the surface of NK cells following activation by interleukin-2 (IL-2), a cytokine that promotes NK cell proliferation and activation. CD137, also known as 4-1BB, is a costimulatory receptor that is upregulated on activated NK cells and promotes their survival and proliferation. CD107a, also known as lysosomal-associated membrane protein 1 (LAMP-1), is a marker that is expressed on the surface of NK cells following degranulation, a process by which cytotoxic molecules are released to kill target cells.

Besides surface markers, cytokines produced by activated NK cells can also be used to identify and characterize these cells. Interferon-gamma (IFN-γ) is a cytokine produced by activated NK cells that regulate adaptive immune responses. Tumor necrosis factor alpha (TNF-α) is another cytokine produced by activated NK cells that regulates inflammation and apoptosis. Overall, the identification and characterization of activation markers of NK cells are vital for understanding their functions and developing targeted immunotherapies.