Recognition of a virus-encoded ligand by a natural killer cell activation receptor.
Natural killer (NK) cells express inhibitory and activation receptors that recognize MHC class I-like molecules on target cells. These receptors may be involved in the critical role of NK cells in controlling initial phases of certain viral infections. Indeed, the Ly49H NK cell activation receptor confers in vivo genetic resistance to murine cytomegalovirus (MCMV) infections, but its ligand was previously unknown. Herein, we use heterologous reporter cells to demonstrate that Ly49H recognizes MCMV-infected cells and a ligand encoded by MCMV itself. Exploiting a bioinformatics approach to the MCMV genome, we find at least 11 ORFs for molecules with previously unrecognized features of predicted MHC-like folds and limited MHC sequence homology. We identify one of these, m157, as the ligand for Ly49H. m157 triggers Ly49H-mediated cytotoxicity, and cytokine and chemokine production by freshly isolated NK cells. We hypothesize that the other ORFs with predicted MHC-like folds may be involved in immune evasion or interactions with other NK cell receptors.
Smith
Hamish R C
HR
Howard Hughes Medical Institute, and Division of Rheumatology, Department of Medicine, Washington University School of Medicine, and Barnes-Jewish Hospital, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Heusel
Jonathan W
JW
Mehta
Indira K
IK
Kim
Sungjin
S
Dorner
Brigitte G
BG
Naidenko
Olga V
OV
Iizuka
Koho
K
Furukawa
Hiroshi
H
Beckman
Diana L
DL
Pingel
Jeanette T
JT
Scalzo
Anthony A
AA
Fremont
Daved H
DH
Yokoyama
Wayne M
WM
D000818:Animals; D007694:Killer Cells, Natural / Q000276:immunology*; D008024:Ligands; D051379:Mice; D018146:Muromegalovirus / Q000276:immunology*; D016366:Open Reading Frames; D011956:Receptors, Cell Surface / Q000276:immunology*
D008024:Ligands; D011956:Receptors, Cell Surface