ULBP/RAET1 Anticorpi

Natural killer (NK) cells attack tumor and infected cells, but the receptors and ligands that stimulate them are poorly understood. Two murine ligands for the lectin-like receptor NKG2D, H60 and retinoic acid early inducible (Rae-1å, ∫, ©, ∂ and é), are distant relatives of major histocompatibility complex class I molecules. Expression of the NKG2D ligands is low or absent on normal, adult tissues; however, they are constitutively expressed on some tumors and upregulated by retinoic acid. Ectopic expression of Rae-1 and H60 confers target susceptibility to NK cell attack. NKG2D binds to H60 with approximately 25-fold higher affinity than to Rae-1. Rae-1 and H60 compete directly for occupancy of NKG2D; therefore, NKG2-D can be occupied by only one ligand at a time. Additionally, Rae-1 and H60 ligands of the NKG2-D receptor stimulate tumor immunity. Cytomegalovirus UL16 binding proteins, known as ULBPs, are GPI-linked glycoproteins that belong to the extended MHC class I family and are distantly related to MHC class I polypeptide-related sequence B, known as MICB. ULBP and MICB proteins are ligands for the activating receptor NKG2D/DAP10, which causes lymphocyte activation resulting in the secretion of cytokines, such as interferon-gamma, and tumor cell lysis. The interaction of ULBP or MICB with NKG2D/DAP10 can be blocked by the soluble form of UL16. ULBPs stimulate cytokine and chemokine production from NK cells, CD8 alpha/beta T cells, and gamma/delta T cells.