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Natural killing of xenogeneic cells mediated by the mouse Ly-49D receptor
M C Nakamura1, C Naper, E C Niemi
1Department of Medicine, Veterans Administration Medical Center, University of California, San Francisco 94121, USA. marynak@itsa.ucsf.edu
Abstract:
NK lymphocytes lyse certain xenogeneic cells without prior sensitization. The receptors by which NK cells recognize xenogeneic targets are largely uncharacterized but have been postulated to possess broad specificity against ubiquitous target ligands. However, previous studies suggest that mouse NK cells recognize xenogeneic targets in a strain-specific manner, implicating finely tuned, complex receptor systems in NK xenorecognition. We speculated that mouse Ly-49D, an activating NK receptor for the MHC I ligand, H2-Dd, might display public specificities for xenogeneic target structures. To test this hypothesis, we examined the lysis of xenogeneic targets by mouse Ly-49D transfectants of the rat NK cell line RNK-16 (RNK. Ly-49D). Of the xenogeneic tumor targets tested, RNK.Ly-49D, but not untransfected RNK-16, preferentially lysed tumor cells derived from Chinese hamsters and lymphoblast targets from rats. Ly-49D-dependent recognition of Chinese hamster cells was independent of target N-linked glycosylation. Mouse Ly-49D also specifically stimulated the natural killing of lymphoblast targets derived from wild-type and MHC-congenic rats of the RT1lv1 and RT1l haplotypes, but not of the RT1c, RT1u, RT1av1, or RT1n haplotypes. These studies demonstrate that Ly-49D can specifically mediate cytotoxicity against xenogeneic cells, and they suggest that Ly-49D may recognize xenogeneic MHC-encoded ligands.
Insights
Mouse Ly-49D, an activating natural killer (NK) cell receptor, can specifically kill xenogeneic cells. This suggests Ly-49D recognizes foreign MHC-encoded ligands on target cells.
Area of Science:
- Immunology
- Cellular and Molecular Immunology
Background:
- Natural killer (NK) cells lyse xenogeneic cells without prior sensitization.
- NK cell receptors for xenogeneic targets are poorly understood, though some suggest broad specificity.
- Previous research indicates mouse NK cells recognize xenogeneic targets in a strain-specific manner, implying complex receptor systems.
Purpose of the Study:
- To investigate if mouse Ly-49D, an activating NK receptor, recognizes xenogeneic target structures.
- To test the hypothesis that Ly-49D possesses public specificities for xenogeneic targets.
Main Methods:
- Transfected rat NK cell line RNK-16 with mouse Ly-49D (RNK.Ly-49D).
- Assessed lysis of various xenogeneic tumor and lymphoblast targets by RNK.Ly-49D and untransfected RNK-16 cells.
- Determined if Ly-49D recognition of Chinese hamster cells was dependent on N-linked glycosylation.
- Examined Ly-49D-mediated cytotoxicity against rat lymphoblast targets from different MHC haplotypes.
Main Results:
- RNK.Ly-49D cells preferentially lysed Chinese hamster tumor cells and rat lymphoblast targets, unlike untransfected RNK-16 cells.
- Ly-49D-dependent lysis of Chinese hamster cells was not affected by target N-linked glycosylation.
- Mouse Ly-49D specifically stimulated natural killing of rat lymphoblasts expressing RT1lv1 and RT1l MHC haplotypes, but not others.
Conclusions:
- Mouse Ly-49D can mediate specific cytotoxicity against xenogeneic cells.
- These findings suggest Ly-49D may recognize xenogeneic MHC-encoded ligands.