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
| Autor: | Ronald J. Plishka, Jamie Rossjohn, Dan Chen, Ranjini Iyengar, Andrew G. Brooks, Alicia Buckler-White, Bernard A. P. Lafont, Emma Gostick, David Price, Julian P. Vivian, Sebastien M. Maloveste, Robin L. Kruthers |
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| Rok vydání: | 2012 |
| Předmět: |
Amino Acid Motifs
Immunology chemical and pharmacologic phenomena Major histocompatibility complex Macaque Article Cell Line Interleukin 21 biology.animal MHC class I Animals Humans Immunology and Allergy Receptor Cells Cultured biology Degranulation Receptors KIR3DL1 Virology Cell biology Killer Cells Natural HLA-B Antigens Cell culture biology.protein Interleukin 12 Macaca nemestrina Protein Binding |
| Zdroj: | The Journal of Immunology. 189:4338-4348 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1201360 |
| Popis: | The killer cell immunoglobulin-like receptors (KIRs) expressed on the surface of natural killer (NK) cells recognize specific major histocompatibility complex class I (MHC-I) molecules and regulate NK cell activities against pathogen-infected cells and neoplasia. In human immunodeficiency virus (HIV) infection, survival is linked to host KIR and MHC-I genotypes. In the simian immunodeficiency virus (SIV) macaque model, however, the role of NK cells is unclear due to the lack of information on KIR-MHC interactions. Here, we describe the first characterization of a KIR-MHC interaction in pig-tailed 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. |
| Databáze: | OpenAIRE |
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