The report has been accepted by the scientific community along with two additional reports (Lee et al., Nature Genetics 28:42, 2001; Daniels et al., J. Exp. Med. 194:29, 2001) that together demonstrated that the Ly49H natural killer (NK) cell surface receptor is absolutely required by NK cells from C57BL/6 mice to contain virus replication and for survival following infection with murine cytomegalovirus (MCMV).

This discovery identified a key NK cell surface receptor (Ly49H) as mediating resistance to an important viral pathogen—murine cytomegalovirus (MCMV).

This paper was the culmination of over a decade’s worth of effort to identify the molecule mediating resistance to murine cytomegalovirus (MCMV). The resistance phenotype, Cmv1, was originally identified by Scalzo et al. (J. Exp. Med. 171:1469, 1990) and was shown to be mediated through NK cells. More importantly, since Cmv1 turned out to be an activating surface receptor on NK cells (Ly49H), this research identified one of the first physiologic mechanisms for NK cell activation, providing an excellent model in which to understand these enigmatic lymphocytes.

I joined Dr. Wayne M. Yokoyama’s research team at the Mount Sinai Medical Center in New York City in 1993. At that time, Dr. Yokoyama’s team studied cell surface protein receptors on NK cells and their role in controlling NK cell activity. After my arrival, I became more interested in understanding how NK cells could actually recognize and destroy virus infected cells, which ultimately led to our identification of the important role of Ly49H as a virus-specific receptor for protective immunity through NK cells.