Effective inhibition of Kb- and Db-restricted antigen presentation in primary macrophages by murine cytomegalovirus

Diane M. LoPiccolo, Marielle Gold, Daniel G. Kavanagh, Markus Wagner, Ulrich H. Koszinowski, Ann Hill

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Abstract

Macrophages play an important role in murine cytomegalovirus (MCMV) infection in vivo, both in disseminating infection and in harboring latent virus, MCMV encodes three immune evasion genes (m4, m6, and m152) that interfere with the ability of cytotoxic T cells (CTL) to detect virus-infected fibroblasts, but the efficacy of immune evasion in macrophages has been controversial. Here we show that MCMV immune evasion genes function in H-2b primary bone marrow macrophages (BMMΦ) in the same way that they do in fibroblasts. Metabolic labeling experiments showed that class I is retained in the endoplasmic reticulum by MCMV infection and associates with m4/gp34 to a similar extent in fibroblasts and BMMΦ. We tested a series of Kb- and Db-restricted CTL clones specific for MCMV early genes against a panel of MCMV wild-type virus and mutants lacking m152, m4, or m6. MCMV immune evasion genes effectively inhibited antigen presentation. m152 appeared sufficient to abolish Db-restricted presentation in infected macrophages, as has been previously observed in infected fibroblasts. However, for inhibition of recognition of infected macrophages by Kb-restricted CTL, m4, m6, and m152 were all required. The contribution of m4 to inhibition of recognition appeared much more important in macrophages than in fibroblasts. Thus, MCMV immune evasion genes function effectively in primary macrophages to prevent CTL recognition of early antigens and show the same pattern of major histocompatibility complex class I allele discrimination as is seen in fibroblasts. Furthermore, for inhibition of Kb-restricted presentation, a strong synergistic effect was noted among m152, m4, and m6.

Original languageEnglish (US)
Pages (from-to)301-308
Number of pages8
JournalJournal of Virology
Volume77
Issue number1
DOIs
StatePublished - Jan 2003

Fingerprint

Muromegalovirus
Cytomegalovirus
antigen presentation
Antigen Presentation
immune evasion
Immune Evasion
macrophages
Macrophages
fibroblasts
Fibroblasts
mice
T-lymphocytes
T-Lymphocytes
Genes
Cytomegalovirus Infections
Viruses
genes
bone marrow
viruses
Bone Marrow

ASJC Scopus subject areas

  • Immunology

Cite this

Effective inhibition of Kb- and Db-restricted antigen presentation in primary macrophages by murine cytomegalovirus. / LoPiccolo, Diane M.; Gold, Marielle; Kavanagh, Daniel G.; Wagner, Markus; Koszinowski, Ulrich H.; Hill, Ann.

In: Journal of Virology, Vol. 77, No. 1, 01.2003, p. 301-308.

Research output: Contribution to journalArticle

LoPiccolo, Diane M. ; Gold, Marielle ; Kavanagh, Daniel G. ; Wagner, Markus ; Koszinowski, Ulrich H. ; Hill, Ann. / Effective inhibition of Kb- and Db-restricted antigen presentation in primary macrophages by murine cytomegalovirus. In: Journal of Virology. 2003 ; Vol. 77, No. 1. pp. 301-308.
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