Document Detail


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.
MedLine Citation:
PMID:  23041569     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Sebastien M Maloveste; Dan Chen; Emma Gostick; Julian P Vivian; Ronald J Plishka; Ranjini Iyengar; Robin L Kruthers; Alicia Buckler-White; Andrew G Brooks; Jamie Rossjohn; David A Price; Bernard A P Lafont
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-10-05
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  189     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-22     Completed Date:  2013-01-09     Revised Date:  2013-11-06    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4338-48     Citation Subset:  AIM; IM    
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.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Motifs / immunology
Animals
Cell Line
Cells, Cultured
HLA-B Antigens / chemistry,  metabolism
Humans
Killer Cells, Natural / immunology*,  metabolism*
Macaca nemestrina
Protein Binding / immunology
Receptors, KIR3DL1 / biosynthesis,  genetics*,  metabolism*
Grant Support
ID/Acronym/Agency:
ZIA AI001026-04/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/HLA-B Antigens; 0/HLA-Bw4 antigen; 0/HLA-Bw6 antigen; 0/Receptors, KIR3DL1
Comments/Corrections

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