Recombinant Mouse ULBP-1/MULT-1 Protein

MULT-1 (mouse UL16-binding protein-like Transcript 1) is a 53 kDa, MHC Class I-like molecule that belongs to the mouse family of NKG2D ligands (1-4). It is a type I transmembrane glycoprotein that is synthesized as a 334 amino acid (aa) precursor. It contains a 25 aa signal sequence, a 186 aa extracellular region, a 19 aa transmembrane segment and a 104 aa cytoplasmic tail (2). The extracellular region contains an alpha-1 and alpha-2 like domain with two intrachain disulfide bonds. MULT-1 is distantly related to other human and mouse NKG2D ligands, and more distantly related to the MHC class I proteins (3). Unlike most NKG2D ligands, transcripts for MULT-1 have been detected in a wide variety of mouse tissues and tumor cells lines (3). The receptor for MULT-1 is NKG2D, a 35 kDa C-type lectin that is found on mouse NK cells, activated CD8⁺ T cells, epidermal gamma delta T cells, and activated macrophages (1, 5, 6, 7). Recombinant MULT-1 protein binds to NKG2D with high affinity (K_d = 6 nM) (2). Although an activating receptor, general cellular responses to NKG2D ligation depend upon the isoform of NKG2D and the cell type (5). Little is known about the specific MULT-1-NKG2D association. Exposure to immobilized MULT-1 or MULT-1-transfected cells elicits IFN-gamma production by NK cells (3). Ectopic expression of MULT-1 on the RMA mouse tumor cell line leads to tumor rejection in syngeneic mice (3).