MHC H-2k prompts Ly49G2+ NK cell responsiveness to murine cytomegalovirus and acquisition of virus-specific effector T cells (44.16)

Abstract

Abstract An MHC H-2k locus is critical in NK cell-mediated resistance to murine CMV (MCMV) in MA/My mice. Recently we found that congenic mouse strains C57L.M-H2k(R7) and C57L.M-H2k(R2) which express different MHC class I D alleles, also exhibit remarkable variation in MCMV resistance. Interestingly, MCMV resistance (Cmvr) in R7 mice corresponds with selective expansion and activation of inhibitory Ly49G2 receptor bearing NK cells after virus infection. Here we examined a potential role for Ly49G2+ NK cells in MCMV resistance, maintenance of splenic dendritic cell subsets and establishment of virus-specific CD8+ T cells. We show that Ly49G2+ NK cells acquire functional competence most efficiently in Dk-expressing R7 animals. In addition, we have observed a loss of splenic CD8α+ and CD11b+ dendritic cells shortly after MCMV infection in susceptible (Cmvs) R2 mice, whereas R7 animals maintain these subsets. We further report that efficient MHC H-2k NK-mediated virus immunity led to a robust and significant expansion of MCMV-specific CD8 T cells by day 6 in R7 mice in contrast with R2 or C57L (Cmvs) animals, which failed to mount efficient CD8 T cell immune responses. We conclude that MHC H-2k enhances virus specific T cell immunity in R7 congenic mice, in addition to establishing functionally competent Ly49G2+ NK cells, which can rapidly respond to MCMV infection. Supported by NIH R01 AI050072.