title: MHC class I-like genes in cattle, MHCLA, with similarity to genes encoding NK cell stimulatory ligands.
abstract: A comparative genomics approach for mining databases of expressed sequence tags (ESTs) was used to identify two members of a novel MHC class I gene family in cattle. These paralogous genes, named MHC class I-like gene family A1 ( MHCLA1) and MHCLA2, were shown by phylogenetic analysis to be related to human and mouse genes encoding NK cell stimulatory ligands, ULBP, RAET, H60 and Raet-1. Radiation hybrid mapping placed cattle MHCLA1 on BTA9, which, on the basis of existing comparative mapping data, identified the ULBP, RAET1, H60 and Raet1 genes as homologues of the cattle MHCLA genes. However, the human and mouse orthologues of MHCLA1 and MHCLA2 could not be defined due to extensive sequence divergence from all known members of the ULBP1/ RAET1/H60/Raet1 gene family. The cattle MHCLA1 molecule is predicted to be missing an alpha(3) domain, similar to the human and mouse homologues. Like the human ULBP genes, MHCLA1 was found to be transcribed constitutively in a variety of fetal and adult tissues by RT-PCR. The patterns of hybridization obtained by Southern blotting using MHCLA1 as a probe and DNA from 14 species representing five mammalian orders suggests that the MHCLA genes evolved rapidly in the Cetartiodactyla. Previous findings demonstrating that ULBPs serve as ligands for the NK cell NKG2D stimulatory receptor, and that this interaction can be blocked by a human cytomegalovirus glycoprotein that binds to ULBPs, suggests that the extensive divergence found among the cattle, human and mouse MHCLA homologues is due to selection exerted by viral pathogens.
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, 210 Edward R. Madigan Laboratory, 1201 W. Gregory Dr., Urbana, IL 61801, USA.
authors.forename: Joshua H
authors.initials: JH
authors.lastname: Larson
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Rebeiz
authors.forename: Chad M
authors.initials: CM
authors.lastname: Stiening
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Windish
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Beever
authors.forename: Harris A
authors.initials: HA
authors.lastname: Lewin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics; D002417:Cattle / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D015778:Minor Histocompatibility Antigens / Q000235:genetics; D008969:Molecular Sequence Data; D055655:NK Cell Lectin-Like Receptor Subfamily K; D010802:Phylogeny; D012313:RNA / Q000378:metabolism; D021101:Radiation Hybrid Mapping; D011971:Receptors, Immunologic / Q000235:genetics; D055607:Receptors, Natural Killer Cell; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D058851:GPI-Linked Proteins; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D055655:NK Cell Lectin-Like Receptor Subfamily K; C491219:Raet1a protein, mouse; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C423231:ULBP1 protein, human; C114735:minor H antigen H60; D012313:RNA