Positive recognition of MHC class T molecules by the Ly49D receptor of murine NK cells

Members of the murine Ly49 family of receptors have been shown to inhibit and activate NK cell function, Subsets of Ly49-expressing NK cells mediate the rejection of bone marrow cell allografts and the lysis of allogeneic lymphoblasts. In this report we have studied Ly49-mediated positive and negative signaling in an in vitro cytotoxicity assay using sorted NK cell subsets as effecters and a panel of Cr-51-labeled Con A lymphoblasts as targets in the presence or the absence of Abs to Ly49 and/or class I molecules, Our results demonstrate that the activating receptor Ly49D delivers stimulatory signals for target cell lysis upon interacting with H2-D-d, D-r, and D-sp2, but not H2(b) or H2(k) class I Ags, On the other hand, the inhibitory receptor Ly49G2 delivers negative signals for target cell lysis upon interacting with D-d, D-r, and H2(k), but not H2(b) or D-sp2, class I Ags, Furthermore, Ly49-mediated negative signaling dominates Ly49D-mediated positive signaling. Thus, lysis of class I MHC-bearing targets by NK cells is not merely the consequence of the absence of an Ly49-mediated negative signal, but also requires positive recognition of class I molecules by certain Ly49 receptors, Activation of NK cells by nonself Class I molecules was not predicted by the missing self hypothesis. [References: 49]

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