D binding of a soluble type of mouse NKG2D to mouse transformed cell lines and

D binding of a soluble type of mouse NKG2D to mouse transformed cell lines and used expression cloning methods to determine the NKG2D ligands (23,24), which included Rae-1 as well as a related protein name histocompatibility antigen 60 (H60) (25). Presently, you’ll find 5 known members with the Rae-1 household, named Rae-1, Rae-1, Rae-1, Rae-1, and Rae-1, that are differentially expressed in various mouse strains and hugely associated to each other (85 identity). The H60 family members comprises 3 members. H60a, the first ligand on the household to become described, was initially identified as a minor histocompatibility antigen by immunizing C57BL/6 mice with MHCidentical BALB.B cells (25). Recently, making use of the amino sequence of H60a as a query, Takeda et al. and Whang et al. identified two novel members of this loved ones, named H60b and H60c (26,27). Ultimately, Murine UL-16-binding protein-like transcript 1 (MULT1) would be the distinctive member in the third family of mouse NKG2D ligands and was found by database looking for mouse sequences with CCR9 Antagonist drug similarities to human ULBP (28,29).NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptStructural nature of membrane-bound ligandsMouse and human NKG2D ligands are structural homologs of MHC class I molecules but stay a comparatively distantly related family. The NKG2D ligands differ widely in sequence, domain structure, and affinity for the NKG2D receptor (Fig. 2). MICA and MICB are encoded within the human MHC, with which they share 285 sequence homology. Similarly to MHC class I molecules, MICA and MICB possess 3 immunoglobulin (Ig)-like domains (1, two, and three) and have a quick cytoplasmic tail. As opposed to MHC molecules, MICA and MICB usually do not associate with 2-microglobulin or bind peptides. Indeed, the 1 and 2 domains lack the important residues in standard MHC class I molecules which have been shown to interact with antigenic peptides. The other mouse and human NKG2D ligands are structurally equivalent to MIC, but lack the 3 domain (Fig. 2). NKG2D ligands differ inside the way they’re attached to the membrane. Human ULBP1, ULBP2, ULBP3, and ULBP6 and mouse Rae-1- and H60c are attached for the cell surface membrane by way of glycosylphosphatidylinositol (GPI) anchors. Human MICA, MICB, ULPB4, and ULBP5 and mouse H60a and H60b are Aurora C Inhibitor web transmembrane proteins and have cytoplasmic tails of varying length and sequences. It has been suggested that the membrane anchorage of NKG2D ligands might impact their affinity for lipid rafts (30). Especially, the GPI-anchored ULBP1, ULBP2, and ULBP3 glycoproteins are constitutively present in lipid rafts, whereas the transmembrane domain-containing MICA is just not (30). NKG2D ligands are highly polymorphic, especially MICA and MICB genes for which 70 and 31 alleles have already been described, respectively (http://www.ebi.ac.uk/imgt/hla/align.html). There is also proof for some degree of polymorphism in the mouse Raet1 and H60 genes, at the same time because the human RAET1 genes and promoter sequences (31,32). Interestingly, allelic variants of these ligands have been shown to bind with variable affinity to NKG2D (33,34).Immunol Rev. Author manuscript; available in PMC 2011 May perhaps 1.Champsaur and LanierPageDiversity of ligands driven by viral pressureThere is ample evidence of pathogens driving the diversity of NKG2D ligands. Viruses have evolved many mechanisms to evade NK cells (35), and in distinct NKG2D-mediated viral surveillance. Most examples of NKG2D evasion mechanisms come from the study of human an.