Recognition of a virus-encoded ligand by a natural killer cell activation receptor

Hamish R.C. Smith, Jonathan W. Heusel, Indira K. Mehta, Sungjin Kim, Brigitte G. Dorner, Olga V. Naidenko, Koho Iizuka, Hiroshi Furukawa, Diana L. Beckman, Jeanette T. Pingel, Anthony A. Scalzo, Daved H. Fremont, Wayne M. Yokoyama

Research output: Contribution to journalArticlepeer-review

619 Scopus citations


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.

Original languageEnglish
Pages (from-to)8826-8831
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number13
StatePublished - Jun 25 2002


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