title: Pig-tailed macaques (Macaca nemestrina) possess six MHC-E families that are conserved among macaque species: implication for their binding to natural killer receptor variants.
abstract: MHC loci encode highly polymorphic molecules involved in the presentation of self and non-self peptides to cells of the adaptive and innate immune systems. Although variable, MHC-E genes are well conserved among primates and provide signals to natural killer cells. In this study, we sequenced and analyzed MHC-E alleles of pig-tailed macaque (Macaca nemestrina), a nonhuman primate used for HIV pathogenesis and vaccine studies. Among a group of seven macaques, the characterization of eight Mane-E alleles revealed an increased number of polymorphic sites compared with human HLA-E alleles. Phylogenetic analyses of MHC-E alleles from pig-tailed macaque, rhesus monkey (Macaca mulatta) and cynomolgus macaque (Macaca fascicularis) demonstrated that the three macaque species shared six families of macaque MHC-E alleles and indicated that these families existed in the common ancestor 5.5 million years ago. Polymorphic Mane-E sites were not concentrated within the peptide-binding pockets, but were distributed throughout the entire ORF. The peptide-binding domain of Mane-E is similar to its human analogue, and peptide substrates theoretically capable of binding to Mane-E molecules were found in the leader sequence of classical Mane-A and -B molecules. Additionally, the polymorphic amino acids located in the alpha(1) and alpha(2) domains of Mane-E molecules have side chains expected to be oriented toward solvent and away from the peptide-binding groove, suggesting that some of them (positions 19, 73, 79 and 145) might be available for interaction with polymorphic receptors of natural killer cells.
authors.affiliation: Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4 Center Drive, Bethesda, MD 20892, USA.
authors.forename: Bernard A P
authors.initials: BA
authors.lastname: Lafont
authors.forename: Alicia
authors.initials: A
authors.lastname: Buckler-White
authors.forename: Ron
authors.initials: R
authors.lastname: Plishka
authors.forename: Charles
authors.initials: C
authors.lastname: Buckler
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Martin
mesh_terms: D000483:Alleles; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D017124:Conserved Sequence; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008254:Macaca nemestrina / Q000235:genetics*; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011485:Protein Binding; D021382:Protein Sorting Signals; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides; D021382:Protein Sorting Signals; D011971:Receptors, Immunologic