engleski

RAE-1γ ligand expression by MCMV vector promotes induction and maintenance of protective immune memory

NKG2D is lymphocyte-expressed receptor whose ligands are stress-induced proteins structurally related to MHC class I molecules. Engagement of NKG2D on natural killer (NK) cells potentiate NK cell-mediated killing of stressed cells. In addition, its engagement on NK cells leads to NK cells cytokine production, which modulates the intensity of immune response. On CD8 T cells NKG2D has a co- stimulatory role, increasing the magnitude of specific immune response. Here we demonstrate the exceptional capacity of mouse CMV (MCMV) expressing NKG2D ligand RAE-1γ to serve as highly protective vaccine-vector. We show that co-expression of RAE-1γ and foreign CD8 T cell epitope in the context of MCMV augmented epitope-specific CD8 T cell response and promoted induction of memory precursor CD8 T cells. Immunization with RAE-1γ expressing MCMV and foreign CD8 T cell epitope resulted in long-term protection against respective pathogen by means of CD8 T cells specific to vectored epitope. Moreover, MCMV expressing RAE-1γ preserved splenic dendritic cells (DCs) and hence rescued their co- stimulatory capacity. Improved antigen presentation was retained also in mice unable to cross-present antigens. Surprisingly, we found that RAE-1γ expressing MCMV vector was highly attenuated and equally protective even in NKG2D deficient mice, suggesting additional, NKG2D independent immune function of RAE1γ.

MCMV; CD8 T cell vaccine vector; NKG2D

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