The MHC class I molecule H-2Dp inhibits murine NK cells via the inhibitory receptor Ly49A.
MHC class I molecules strongly influence the phenotype and function of mouse NK cells. NK cell-mediated lysis is prevented through the interaction of Ly49 receptors on the effector cell with appropriate MHC class I ligands on the target cell. In addition, host MHC class I molecules have been shown to modulate the in vivo expression of Ly49 receptors. We have previously reported that H-2Dd and H-2Dp MHC class I molecules are able to protect (at the target cell level) from NK cell-mediated lysis and alter the NK cell specificity (at the host level) in a similar manner, although the mechanism behind this was not clear. In this study, we demonstrate that the expression of both H-2Dd and H-2Dp class I molecules in target cells leads to inhibition of B6 (H-2b)-derived Ly49A+ NK cells. This inhibition could in both cases be reversed by anti-Ly49A Abs. Cellular conjugate assays showed that Ly49A-expressing cells indeed bind to cells expressing H-2Dp. The expression of Ly49A and Ly49G2 receptors on NK cells was down-regulated in H-2Dp-transgenic (B6DP) mice compared with nontransgenic B6 mice. However, B6DP mice expressed significantly higher levels of Ly49A compared with H-2Dd-transgenic (D8) mice. We propose that both H-2Dd and H-2Dp MHC class I molecules can act as ligands for Ly49A.
Olsson-Alheim
M Y
MY
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden. mats.alheim@mtc.ki.se
Sundbäck
J
J
Kärre
K
K
Sentman
C L
CL
D000818:Animals; D000950:Antigens, Ly; D002352:Carrier Proteins / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D064532:Histocompatibility Antigen H-2D; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011485:Protein Binding / Q000276:immunology; D011971:Receptors, Immunologic / Q000502:physiology*; D055630:Receptors, NK Cell Lectin-Like; D014162:Transfection / Q000276:immunology; D019076:Transgenes / Q000276:immunology; D014407:Tumor Cells, Cultured
D000950:Antigens, Ly; D002352:Carrier Proteins; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D007166:Immunosuppressive Agents; C527088:Klra1 protein, mouse; D037181:Lectins, C-Type; D008565:Membrane Proteins; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like