CD244, also known as 2B4, is a cell surface glycoprotein that plays a crucial role in the regulation of natural killer (NK) and T lymphocyte function. It is a member of the signaling lymphocyte activation molecule (SLAM)-related receptor family and is involved in stimulating NK cell cytotoxicity and cytokine production . CD244 is expressed on all NK cells, a subpopulation of T cells, monocytes, and basophils .
CD244 is a transmembrane protein that belongs to the CD2 subset of the immunoglobulin (Ig) superfamily . It primarily binds to its ligand, CD48, on adjacent cells, transmitting stimulatory or inhibitory signals that regulate immune function . The interaction between CD244 and CD48 is essential for the expansion and activation of NK cells . In the absence of this interaction, NK cytotoxicity and IFN-γ secretion are severely impaired .
Recombinant human CD244 is typically produced using DNA sequences encoding the extracellular domain of the protein. For example, a DNA sequence encoding the extracellular domain (Met 1-Arg 221) of human 2B4 can be expressed with a polyhistidine tag at the C-terminus . The recombinant protein is then purified and lyophilized for storage . It is often produced in HEK293 cells and formulated in sterile PBS, pH 7.4, with added protectants such as trehalose, mannitol, and Tween80 .
CD244 is involved in various immune responses, including cytotoxicity, cytokine production, and intercellular interactions . The interaction between CD244 and CD48 on NK cells is crucial for their activation and function . CD244 can also bind to other low-affinity ligands such as CD229, although most studies focus on the CD244-CD48 interaction . The intracellular SLAM-associated protein (SAP) interacts with CD244 via its immunoreceptor tyrosine-based switch motifs (ITSMs), regulating various immune responses .
CD244 provides both stimulatory and inhibitory signals that regulate immune responses in NK cells, CD8+ T cells, and other immune cells . These signals are crucial for the onset and progression of multiple immune-related diseases, including autoimmune diseases, infectious diseases, and cancers . CD244 can act as an immune checkpoint, regulating the immune response and killing tumor cells . It is also used in the construction of chimeric antigen receptors (CARs) on NK cells for adoptive immunotherapy .