title: Two novel NKG2D ligands of the mouse H60 family with differential expression patterns and binding affinities to NKG2D.
abstract: H60, originally described as a dominant minor histocompatibility Ag, is an MHC class I-like molecule that serves as a ligand for the NKG2D receptor. In the present study, we identified two novel mouse chromosome 10-encoded NKG2D ligands structurally resembling H60. These ligands, which we named H60b and H60c, encode MHC class I-like molecules with two extracellular domains. Whereas H60b has a transmembrane region, H60c is a GPI-anchored protein. Recombinant soluble H60b and H60c proteins bound to NKG2D with affinities typical of cell-cell recognition receptors (K(d) = 310 nM for H60b and K(d) = 8.7 muM for H60c). Furthermore, expression of H60b or H60c rendered Ba/F3 cells susceptible to lysis by NK cells, thereby establishing H60b and H60c as functional ligands for NKG2D. H60b and H60c transcripts were detected only at low levels in tissues of healthy adult mice. Whereas H60b transcripts were detectable in various tissues, H60c transcripts were detected mainly in the skin. Infection of mouse embryonic fibroblasts with murine cytomegalovirus induced expression of H60b, but not H60c or the previously known H60 gene, indicating that transcriptional activation of the three types of H60 genes is differentially regulated. The present study adds two new members to the current list of NKG2D ligands.
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, North-15 West-7, Sapporo, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Takada
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yoshida
authors.forename: Mizuho
authors.initials: M
authors.lastname: Kajikawa
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Miyatake
authors.forename: Utano
authors.initials: U
authors.lastname: Tomaru
authors.forename: Masaharu
authors.initials: M
authors.lastname: Sakai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Chiba
authors.forename: Katsumi
authors.initials: K
authors.lastname: Maenaka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kohda
authors.forename: Kazunori
authors.initials: K
authors.lastname: Fugo
authors.forename: Masanori
authors.initials: M
authors.lastname: Kasahara
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002874:Chromosome Mapping; D002875:Chromosomes / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D006566:Herpesviridae Infections / Q000235:genetics / Q000276:immunology; D008024:Ligands; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D018146:Muromegalovirus; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D014158:Transcription, Genetic
chemical_list: D018076:DNA, Complementary; C527292:H60b protein, mouse; C527293:H60c protein, mouse; C527086:Klrk1 protein, mouse; D008024:Ligands; D015778:Minor Histocompatibility Antigens; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C114735:minor H antigen H60