Interactions of Ly49 family receptors with MHC class I ligands in trans and cis.
The Ly49A NK cell receptor interacts with MHC class I (MHC-I) molecules on target cells and negatively regulates NK cell-mediated target cell lysis. We have recently shown that the MHC-I ligand-binding capacity of the Ly49A NK cell receptor is controlled by the NK cells' own MHC-I. To see whether this property was unique to Ly49A, we have investigated the binding of soluble MHC-I multimers to the Ly49 family receptors expressed in MHC-I-deficient and -sufficient C57BL/6 mice. In this study, we confirm the binding of classical MHC-I to the inhibitory Ly49A, C and I receptors, and demonstrate that detectable MHC-I binding to MHC-I-deficient NK cells is exclusively mediated by these three receptors. We did not detect significant multimer binding to stably transfected or NK cell-expressed Ly49D, E, F, G, and H receptors. Yet, we identified the more distantly related Ly49B and Ly49Q, which are not expressed by NK cells, as two novel MHC-I receptors in mice. Furthermore, we show using MHC-I-sufficient mice that the NK cells' own MHC-I significantly masks the Ly49A and Ly49C, but not the Ly49I receptor. Nevertheless, Ly49I was partly masked on transfected tumor cells, suggesting that the structure of Ly49I is compatible in principal with cis binding of MHC-I. Finally, masking of Ly49Q by cis MHC-I was minor, whereas masking of Ly49B was not detected. These data significantly extend the MHC-I specificity of Ly49 family receptors and show that the accessibility of most, but not all, MHC-I-binding Ly49 receptors is modulated by the expression of MHC-I in cis.
Scarpellino
Léonardo
L
Ludwig Institute for Cancer Research, Lausanne Branch; University of Lausanne, Epalinges, Switzerland.
Oeschger
Franziska
F
Guillaume
Philippe
P
Coudert
Jérôme D
JD
Lévy
Frédéric
F
Leclercq
Georges
G
Held
Werner
W
D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D008810:Mice, Inbred C57BL; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000378:metabolism; D055630:Receptors, NK Cell Lectin-Like
D000950:Antigens, Ly; D015395:Histocompatibility Antigens Class I; C527088:Klra1 protein, mouse; C527089:Klra17 protein, mouse; C527090:Klra2 protein, mouse; C527091:Klra3 protein, mouse; C527092:Klra4 protein, mouse; D037181:Lectins, C-Type; D008024:Ligands; C408248:Ly49I antigen; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like