Positive recognition of MHC class I 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 effectors and a panel of 51Cr-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-Dd, Dr, and Dsp2, but not H2b or H2k class I Ags. On the other hand, the inhibitory receptor Ly49G2 delivers negative signals for target cell lysis upon interacting with Dd, Dr, and H2k, but not H2b or Dsp2, 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.
George
T C
TC
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Mason
L H
LH
Ortaldo
J R
JR
Kumar
V
V
Bennett
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D000950:Antigens, Ly; D002469:Cell Separation; D003208:Concanavalin A / Q000276:immunology; D003429:Cross Reactions; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D055630:Receptors, NK Cell Lectin-Like; D013045:Species Specificity