MHC class I alloantigen specificity of Ly-49+ IL-2-activated natural killer cells.
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 cells. In general, target cell major histocompatibility complex (MHC) class I antigen expression correlates with resistance to NK cell-mediated lysis, possibly because NK cell-surface molecules engage MHC class I antigens and consequently deliver inhibitory signals. Natural killer cell allospecificity involves the MHC class I peptide-binding cleft, and further understanding of this allospecificity should provide insight into the molecular mechanisms of NK cell recognition. The Ly-49 cell surface molecular mechanisms of NK cell recognition. The Ly-49 cell surface molecule is expressed by 20% of CD3- NK cells 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 antibodies directed against Ly-49 or the alpha 1/alpha 2 domains of H-2Dd, suggesting that Ly-49 specifically interacts with the peptide-binding domains of the MHC class I alloantigen, H-2Dd. Inasmuch 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.
Karlhofer
F M
FM
Rosalind Russell Arthritis Research Laboratory, Department of Medicine, University of California, San Francisco.
Ribaudo
R K
RK
Yokoyama
W M
WM
D000818:Animals; D000950:Antigens, Ly / Q000032:analysis; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D051379:Mice; D014162:Transfection
D000950:Antigens, Ly; D006183:H-2 Antigens