Natural killer (NK) cells have many receptors, at least two of which—FcγR and DNAM-1—recognize antibody-decorated, virus-infected target cells: the antibodies bound to the infected cells are detected through FcγR, and a protein called CD122 on the surface of the infected cells is detected through DNAM-1. Vaccination with a glycoprotein D-expressing virus (gD+; left) induces predominantly neutralizing antibodies specific for glycoprotein D (green). Upon challenge with HSV, these antibodies bind strongly to the virus but may not bind well to the surface of the virus-infected cell. Consequently, the NK cell FcγRs are not engaged and binding of the NK cell's DNAM-1 to CD122 is not sufficient to induce the killing (by lysis) of the infected cell. In contrast, Petro, González et al. found that vaccination with a gD-deficient virus (gD−; right) induces the production of primarily non-neutralizing antibodies that are specific for a variety of glycoproteins on the surface of the virus. The antibodies in the gD−-vaccinated mouse bind poorly to HSV but strongly to the surface of the infected cells. The NK cells can therefore detect the infected cells through both FcγR and DNAM-1, which is sufficient to activate the NK cells to kill the target cells by lysis.