Macrophages escape inhibition of major histocompatibility complex class I-dependent antigen presentation by cytomegalovirus

The mouse cytomegalovirus (MCMV) m152- and m06-encoded glycoproteins gp40 a nd gp48, respectively, independently downregulate major histocompatibility complex (MHC) class I surface expression during the course of productive MC MV infection in fibroblasts. As a result, presentation of an immediate-earl y protein pp89-derived nonapeptide to H-2L(d)-restricted CD8(+) cytotoxic T cells is completely prevented in fibroblasts. Here,ve demonstrate that MCM V-infected primary bone marrow macrophages and the macrophage cell line J77 4 constitutively present pp89 peptides during permissive MCMV infection to cytotoxic T lymphocytes (CTL). In contrast to fibroblasts, expression of th e m152 and m06 genes in macrophages does not affect surface expression of M HC class I. Assessment of pp89 synthesis and quantification of extracted pe ptide revealed a significantly higher efficiency of macrophages than of fib roblasts to process pp89 into finally trimmed peptide. The yield of pp89 pe ptide determined in MCMV-infected tissues of bone marrow chimeras confirmed that bone marrow-derived cells represent a prime source of pp89 processing in parenchymal organs. The finding that macrophages resist the viral contr ol of MHC I-dependent antigen presentation reconciles the paradox of effici ent induction of CMV-specific CD8(+) CTL in vivo despite extensive potentia l of CMVs to subvert MHC class I.