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

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 AP Lafont

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18 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)4338 - 4348
Number of pages11
JournalJournal of Immunology
Volume189
Issue number9
DOIs
Publication statusPublished - 2012

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