Quantifying the reduction in accessibility of the inhibitory NK cell receptor Ly49A caused by binding MHC class I proteins in cis.
Murine natural killer (NK) cells are inhibited by target cell MHC class I molecules via Ly49 receptors. However, Ly49 receptors can be made inaccessible to target cell MHC class I by a cis interaction with its MHC class I ligand within the NK cell membrane. It has recently been demonstrated that MHC class I proteins transfer from the target cells to the NK cell. Here, we establish that the number of transferred MHC class I proteins is proportional to the number of Ly49A receptors at the NK cell surface. Ly49A+ NK cells from mice expressing the Ly49A ligand H-2D(d) showed a 90% reduction in Ly49A accessibility compared to Ly49A+ NK cells from H-2D(d)-negative mice. The reduction was caused both by lower expression of Ly49A and interactions in cis between Ly49A and H-2D(d) at the NK cell surface. Approximately 75% of the Ly49A receptors on H-2D(d)-expressing NK cells were occupied in cis with endogenous H-2D(d) and only 25% were free to interact with H-2D(d) molecules in trans. Thus, H-2D(d) ligands control Ly49A receptor accessibility through interactions both in cis and in trans.
Andersson
Katja E
KE
Department of Microbiology, Tumor and Cell Biology and the IRIS Strategic Research Center, Karolinska Institute, Stockholm, Sweden.
Williams
Geoffrey S
GS
Davis
Daniel M
DM
Höglund
Petter
P
D000818:Animals; D000950:Antigens, Ly / Q000737:chemistry* / Q000276:immunology; D018920:Coculture Techniques; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000737:chemistry* / Q000276:immunology; D064532:Histocompatibility Antigen H-2D; D006863:Hydrogen-Ion Concentration; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011485:Protein Binding / Q000276:immunology; D055630:Receptors, NK Cell Lectin-Like
D000950:Antigens, Ly; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; C527088:Klra1 protein, mouse; D037181:Lectins, C-Type; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055630:Receptors, NK Cell Lectin-Like