title: Degenerate recognition of MHC class I molecules with Bw4 and Bw6 motifs by a killer cell Ig-like receptor 3DL expressed by macaque NK cells.
abstract: The killer cell Ig-like receptors (KIRs) expressed on the surface of NK cells recognize specific MHC class I (MHC-I) molecules and regulate NK cell activities against pathogen-infected cells and neoplasia. In HIV infection, survival is linked to host KIR and MHC-I genotypes. In the SIV macaque model, however, the role of NK cells is unclear due to the lack of information on KIR-MHC interactions. In this study, we describe, to our knowledge, the first in-depth characterization of KIR-MHC interactions in pigtailed macaques (Macaca nemestrina). Initially, we identified three distinct subsets of macaque NK cells that stained ex vivo with macaque MHC-I tetramers loaded with SIV peptides. We then cloned cDNAs corresponding to 15 distinct KIR3D alleles. One of these, KIR049-4, was an inhibitory KIR3DL that bound MHC-I tetramers and prevented activation, degranulation, and cytokine production by macaque NK cells after engagement with specific MHC-I molecules on the surface of target cells. Furthermore, KIR049-4 recognized a broad range of MHC-I molecules carrying not only the Bw4 motif, but also Bw6 and non-Bw4/Bw6 motifs. This degenerate, yet peptide-dependent, MHC reactivity differs markedly from the fine specificity of human KIRs.
authors.affiliation: Non-Human Primate Immunogenetics and Cellular Immunology Unit, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Sebastien M
authors.initials: SM
authors.lastname: Maloveste
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.forename: Emma
authors.initials: E
authors.lastname: Gostick
authors.forename: Julian P
authors.initials: JP
authors.lastname: Vivian
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Plishka
authors.forename: Ranjini
authors.initials: R
authors.lastname: Iyengar
authors.forename: Robin L
authors.initials: RL
authors.lastname: Kruthers
authors.forename: Alicia
authors.initials: A
authors.lastname: Buckler-White
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: David A
authors.initials: DA
authors.lastname: Price
authors.forename: Bernard A P
authors.initials: BA
authors.lastname: Lafont
mesh_terms: D020816:Amino Acid Motifs / Q000276:immunology; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D015235:HLA-B Antigens / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008254:Macaca nemestrina; D011485:Protein Binding / Q000276:immunology; D054341:Receptors, KIR3DL1 / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C038652:HLA-Bw6 antigen; D054341:Receptors, KIR3DL1