Abstract
THE molecular basis of target cell recognition by CD3− natural killer (NK) cells is poorly understood, despite the ability of NK cells to lyse specific tumour cells1,2. In general, target cell major histocompatibility complex (MHC) class I antigen expression correlates with resistance to NK cell-mediated lysis3–9, possibly because NK cell-surface molecules engage MHC class I antigens and consequently deliver inhibitory signals3,4. Natural killer cell allospecificity involves the MHC class I peptide-binding cleft10, and further understanding of this allospecificity should provide insight into the molecular mechanisms of NK cell recognition. The Ly-49 cell surface molecule is expressed by 20% of CD3− NK cells11 in C57BL/6 mice (H–2b). Here we show that C57BL/6-derived, interleukin-2-activated NK cells expressing Ly-49 do not lyse target cells displaying H–2d or H–2k despite efficient spontaneous lysis by Ly-49− effector cells. This preferential resistance correlates with expression of target cell MHC class I antigens. Transfection and expression of H–2Dd, but not H–2Kd or H–2Ld, renders a susceptible target (H–2b) resistant to Ly-49+ effector cells. The transfected resistance is abrogated by monoclonal anti-bodies directed against Ly-49 or the α1/α2 domains of H–2Dd, suggesting that Ly-49 specifically interacts with the peptide-binding domains of the MHC class I alloantigen, H–2Dd. Inas-much as Ly-49+ effector cells cannot be stimulated to lyse H–2Dd targets, our results indicate that NK cells may possess inhibitory receptors that specifically recognize MHC class I antigens.
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Karlhofer, F., Ribaudo, R. & Yokoyama, W. MHC class I alloantigen specificity of Ly-49+ IL-2-activated natural killer cells. Nature 358, 66–70 (1992). https://doi.org/10.1038/358066a0
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DOI: https://doi.org/10.1038/358066a0
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