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Work package 2

Characterization of the NKG2D-independent immune function of RAE-1γ

NKG2DandRAESo far, the only known cellular receptor for RAE-1 is NKG2D. However, our recent finding strongly indicates the existence of a new, so far unrecognized, immune function of the NKG2D ligand RAE-1. Specifically, RAE-1γMCMV showed a similar level of attenuation and induction of protective immune response in mice lacking NKG2D receptor as control mice (Trsan et al. Proc Natl Acad Sci USA, 2013). Our preliminary data have shown that conventional dendritic cells (cDCs) derived from both WT and NKG2D-deficient mice, were positive in intracellular staining with RAE-1γ multimer, thus indicating the existence of a RAE-1γ binding partner other than NKG2D. Elucidating additional functions of RAE-1 is essential for our understanding of an improved vaccine property of CMV which expresses this NKG2D ligand. The aim of this WP is to define the molecular basis of the NKG2D independent immune function of RAE-1γ described above.

To further investigate the role of the RAE-1γ protein, we will generate an additional virus construct with the RAE-1γ protein fused to a fluorescent protein label. The expression of RAE-1γ will be analyzed in a series of in vitro and in vivo live imaging setups, such as the kinetic of virally derived RAE-1γ expression, the relationship between RAE-1γ expression and immune response in different organs including the viral titer, lymphocyte activation status and cytokine secretion.