The MEM-238 monoclonal antibody specifically binds to CD222, which is also known as the Insulin-like growth factor 2 Receptor (IGF2R, IGF-II Receptor), Cation-independent mannose 6-phosphate receptor (CIMPR), or Mannose-6 phosphate receptor (M6PR). CD222 is ubiquitously expressed by a variety of cell types as a cell surface type I transmembrane glycoprotein. However, in the course of receptor trafficking between the cell surface and intracellular compartments, the majority of CD222 is found within cells. Cell surface CD222 functions as a multifunctional receptor that binds to a large number of extracellular ligands including acid hydrolases, insulin-like growth factors, latent TGF-β, leukemia inhibitory factor (LIF), proliferin, prorenin, plasminogen, and Herpes simplex virus. It regulates extracellular Insulin-like growth factor II (IGF-II/IGF-2) levels by binding and internalizing the growth factor for lysosomal degradation. This effectively removes IGF-II from the circulation and tissues and thus prevents it from signaling through the growth-stimulatory Insulin-like growth factor I Receptor (IGF-1R, CD221) pathway. However, studies have reported that IGF-II may activate some cellular functions through CD222 as well. A soluble form of the CD222 extracellular region can also be detected in human serum and may play a role in regulating IGF-II activity. CD222 serves as a surface receptor for latent TGFβ and can complex with plasminogen and CD87, a urokinase-type plasminogen activator receptor, to activate latent TGF-β. CD222 also binds to a variety of Mannose 6-phosphate (M6P)-containing proteins, including extracellular and newly-synthesized lysosomal enzymes, and transports them to lysosomes.
The antibody was conjugated to BD Horizon™ BUV563 which is part of the BD Horizon Brilliant™ Ultraviolet family of dyes. This dye is a tandem fluorochrome of BD Horizon BUV395 which has an Ex Max of 348 nm and an acceptor dye. The tandem has an Em Max at 563 nm. BD Horizon BUV563 can be excited by the 355 nm ultraviolet laser. On instruments with a 561 nm Yellow-Green laser, the recommended bandpass filter is 585/15 nm with a 535 nm long pass to minimize laser light leakage. When BD Horizon BUV563 is used with an instrument that does not have a 561 nm laser, a 560/40 nm filter with a 535 nm long pass may be more optimal. Due to the excitation and emission characteristics of the acceptor dye, there may be spillover into the PE and PE-CF594 detectors. However, the spillover can be corrected through compensation as with any other dye combination.