Recognition of a dendritic cell ligand by an MCMV-encoded MHC-I-like protein (154.17)

Abstract

Abstract Mouse cytomegalovirus (MCMV), a valuable model for studying virus-host interactions, encodes several glycoproteins with predicted MHC-I structure, which may function as immunoevasins. We recently determined the crystallographic structure of a member of this family, m153, and showed that this is a cell surface homodimeric protein with structural similarity to MHC-I, which is expressed independently of beta-2m or peptide. To determine the role of m153 in the viral infection of the host, we wished to identify host proteins with which m153 interacts. We constructed both a birA-tagged version of m153 for staining experiments as well as a reporter cell containing the m153 extracellular domain fused to the human T cell receptor zeta chain. Using both approaches we show that CD11c+ splenic dendritic cells (DCs) and bone marrow-derived DCs express a cell surface ligand for m153. To our knowledge this is the first example of a putative viral immunoevasin that targets a DC expressed molecule. We describe our efforts to identify this molecule using a variety of approaches, including antibody blocking, cDNA library screening, and pull-down experiments on DC lysates. Identification of the m153 ligand on DCs offers to elucidate mechanisms the host employs to defend against viral infection, and also to clarify the evolution of viral immunoevasion of the immune response. This research was supported by the Intramural Research Program of the NIH, NIAID.