engleski

NKG2D ligand RAE-1γ expressed by CMV vector promotes antigen presentation to CD8 T cells

Specific CD8 T cell response is a result of an efficient antigen presentation via dendritic cells (DCs), co-stimulatory signals on CD8 T cell receptors and cytokines. Considering that CD8 T cells play essential role in the control of viruses and other intracellular pathogens, CD8 T cell-based vaccines represent an attractive option for vaccine design. Cytomegalovirus (CMV) is one of the most suitable candidates for such a vaccine since it establishes life-long infection which ensures continuous supply of virus specific effector memory CD8 T cells. Having these facts in mind, we have constructed highly attenuated murine CMV (MCMV) expressing NKG2D ligand RAE-1γ and foreign CD8 T cell epitope. Such a recombinant vaccine-vector provided outstanding CD8 T cell- dependent protective capacity against respective pathogens and maintained this specific response long-term (Trsan et al., PNAS 2013). Although it is generally accepted that the ligation of NKG2D receptor augments CD8 T cell response by providing co-stimulatory signals to CD8 T cells, we showed that the enhanced CD8 T cell response induced by MCMV vector expressing RAE-1γ existed even in mice lacking NKG2D receptor, pointing to an additional, NKG2D-independent immune function of RAE-1γ. Our results indicated that RAE-1γ expression in the context of MCMV vector induced improved antigen presentation via DCs to CD8 T cells. Moreover, RAE-1γMCMV vector was efficient even in N-ras deficient mice, otherwise defective in generating memory CD8 T cells, suggesting that RAE-1γ can circumvent this immune deficit. Altogether, RAE-1γ expressing MCMV demonstrated a powerful capacity to serve as a vaccine-vector. We believe that similar vaccine vectors can be employed to combat various intracellular pathogens and tumors. Since RAE-1γ represents a homologue of human NKG2D ligand ULBP2, one can expect that the results obtained with RAE- 1γMCMV vector can be translated to the HCMV vaccine model.

CMV vector; NKG2D; antigen presentation; vaccine vector; CD8 T cells

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