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Journal of Virology, September 2000, p. 7861-7868, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Macrophages Escape Inhibition of Major Histocompatibility Complex Class I-Dependent Antigen Presentation by Cytomegalovirus

Hartmut Hengel,1,* Uwe Reusch,1 Gernot Geginat,2 Rafaela Holtappels,3 Thomas Ruppert,1 Eva Hellebrand,1 and Ulrich H. Koszinowski1

Lehrstuhl Virologie, Max von Pettenkofer-Institut, Ludwig-Maximilians-Universität, 80336 Munich,1 Institut für Medizinische Mikrobiologie und Hygiene, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, 68167 Mannheim,2 and Institut für Virologie, Johannes Gutenberg-Universität Mainz, 55101 Mainz,3 Germany

Received 18 February 2000/Accepted 31 May 2000

The mouse cytomegalovirus (MCMV) m152- and m06-encoded glycoproteins gp40 and gp48, respectively, independently downregulate major histocompatibility complex (MHC) class I surface expression during the course of productive MCMV infection in fibroblasts. As a result, presentation of an immediate-early protein pp89-derived nonapeptide to H-2Ld-restricted CD8+ cytotoxic T cells is completely prevented in fibroblasts. Here we demonstrate that MCMV-infected primary bone marrow macrophages and the macrophage cell line J774 constitutively present pp89 peptides during permissive MCMV infection to cytotoxic T lymphocytes (CTL). In contrast to fibroblasts, expression of the m152 and m06 genes in macrophages does not affect surface expression of MHC class I. Assessment of pp89 synthesis and quantification of extracted peptide revealed a significantly higher efficiency of macrophages than of fibroblasts to process pp89 into finally trimmed peptide. The yield of pp89 peptide 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 control of MHC I-dependent antigen presentation reconciles the paradox of efficient induction of CMV-specific CD8+ CTL in vivo despite extensive potential of CMVs to subvert MHC class I.

* Corresponding author. Present address: Robert Koch Institut, Nordufer 20, 13353 Berlin, Germany. Phone: 49 1888 7542502. Fax: 49 1888 7542328. E-mail: hengelh{at}rki.de.

Journal of Virology, September 2000, p. 7861-7868, Vol. 74, No. 17
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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