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J Exp Med. 2011 May 9;208(5):1105-17. doi: 10.1084/jem.20101831. Epub 2011 Apr 25.

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

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Department of Human Genetics, McGill University, Montreal, Quebec H3A 2T5, Canada.


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.

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