Natural killer cell receptor 2B4 (CD244) (CD244)

Natural killer cell receptor 2B4 (CD244), also known as 2B4 or SLAMF4, is a transmembrane glycoprotein primarily expressed on natural killer (NK) cells and a subset of CD8+ T cells, belonging to the signaling lymphocytic activation molecule (SLAM) family. It functions as a heterophilic receptor that binds CD48 on target cells, regulating NK cell cytotoxicity, activation, and proliferation through both activating and inhibitory signals depending on cellular context, adaptor proteins like SAP, and receptor isoforms. Structurally, it features two Ig-like extracellular domains with a characteristic immunoglobulin V domain fold, including nine β-strands and a noncanonical disulfide bridge stabilizing its ligand-binding region. In disease, 2B4-CD48 interactions are critical for NK-mediated tumor clearance and antiviral responses but contribute to immunodeficiencies like X-linked lymphoproliferative disease when SAP is mutated, impairing control of infections such as EBV. Its bifunctional nature—activating in humans but sometimes inhibitory in mice—poses challenges for therapeutic targeting, with isoforms differing in intracellular tyrosines and CD48 affinity influencing cytotoxic outcomes. No approved drugs directly target 2B4, but its role in immune regulation makes it a potential candidate for immunotherapy in cancer and infections.

Other names

2B4CD244SLAMF4