Distinct MHC class I–dependent NK cell–activating receptors control cytomegalovirus infection in different mouse strains

Recognition of mouse cytomegalovirus (MCMV)–infected cells by activating NK cell receptors was first described in the context of Ly49H, which confers resistance to C57BL/6 mice. We investigated the ability of other activating Ly49 receptors to recognize MCMV-infected cells in mice from various H-2 backgrounds. We observed that Ly49P1 from NOD/Ltj mice, Ly49L from BALB mice, and Ly49D2 from PWK/Pas mice respond to MCMV-infected cells in the context of H-2D(k) and the viral protein m04/gp34. Recognition was also seen in the H-2(d) and/or H-2(f) contexts, depending on the Ly49 receptor examined, but never in H-2(b). Furthermore, BALB.K (H-2(k)) mice showed reduced viral loads compared with their H-2(d) or H-2(b) congenic partners, a reduction which was dependent on interferon γ secretion by Ly49L(+) NK cells early after infection. Adoptive transfer of Ly49L(+), but not Ly49L(−), NK cells significantly increased resistance against MCMV infection in neonate BALB.K mice. These results suggest that multiple activating Ly49 receptors participate in H-2–dependent recognition of MCMV infection, providing a common mechanism of NK cell–mediated resistance against viral infection.