Murine Cytomegalovirus Is Regulated by a Discrete Subset of Natural Killer Cells Reactive with Monoclonal Antibody to Ly49h

Daniels, Keith A.; Devora, Gene; Lai, Wayne C.; O'Donnell, Carey L.; Bennett, Michael; Welsh, Raymond M.

The mapping of the Cmv-1 gene in proximity to the Ly49 loci in C57BL/6 mice has previously led us to question whether NK cell subsets expressing a distinct Ly49 molecule might mediate resistance to MCMV. No NK cell subset has ever been shown to selectively regulate the synthesis of a virus or any other pathogen in vivo. Analyses of cells expressing different Ly49 molecules have been complicated by the fact that each NK cell expresses several different types of Ly49 molecules and that some of the Abs directed against one molecule cross-react with other molecules. To date, Ly49 molecules defined by four different commercially available Abs have been examined in the MCMV system: Ly49A, D, G2, and C and I, which is a pair detected by the same mAb (5E6; reference 21) . No selective role for either subset could be shown in the control of infection (22) . Mice depleted of NK subsets in vivo with mAb to Ly49 A, D, C/I, or G2, or with combinations of two or three anti-Ly49 mAbs tended to be just as resistant to MCMV as untreated mice. Adoptive transfers of any of these subsets into suckling mice protected them against MCMV (22) . This indicated that neither of these Ly49 molecules defined a subset of NK cells required for resistance to MCMV.