Human cytomegalovirus-derived protein UL18 alters the phenotype and function of monocyte-derived dendritic cells

Abstract: Human cytomegalovirus (HCMV) en-codes the MHC class I-like molecule UL18, which binds with high affinity to the leukocyte Ig-like receptor-1 (LIR-1), an inhibitory receptor com-monly expressed on myeloid cells and subsets of NK and T cells. The exact role of UL18 is not known, in particular, in relation to its proposed role in HCMV immune escape. Given the ubiqui-tous expression of LIR-1 on dendritic cells (DCs), we hypothesized that UL18 may affect DC func-tion. To study the effects of UL18 on DC, we made use of UL18 fusion proteins. We demonstrate that UL18 fusion proteins inhibit the chemotaxis of DCs. Furthermore, UL18 interfered with CD40 ligand-induced maturation of DCs, resulting in re-duced allogeneic T cell proliferation. Finally, we demonstrate that UL18 proteins up-regulate the expression of the maturation marker CD83 on im-mature monocyte-derived DCs and induce cyto-kine production. The capacity of UL18 to affect the function and the phenotype of DCs suggests a novel role for this HCMV-derived protein. J. Leu-koc. Biol. 83: 000–000; 2008. Key Words: MHC class I homologue host/pathogen interaction cell trafficking cell surface molecules immune modulatio