The multiple immune-evasion genes of murine cytomegalovirus are not redundant: m4 and m152 inhibit antigen presentation in a complementary and cooperative fashion

D. G. Kavanagh, M. C. Gold, M. Wagner, U. H. Koszinowski, A. B. Hill

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Both human cytomegaloviruses (HCMVs) and murine cytomegaloviruses (MCMVs) encode multiple genes that interfere with antigen presentation by major histocompatibility complex (MHC) class I, and thus protect infected targets from lysis by virus-specific cytotoxic T lymphocytes (CTLs). HCMV has been shown to encode four such genes and MCMV to encode two. MCMV m152 blocks the export of class I from a pre-Golgi compartment, and MCMV m6 directs class I to the lysosome for degradation. A third MCMV gene, m4, encodes a glycoprotein which is expressed at the cell surface in association with class I. Here we here show that m4 is a CTL-evasion gene which, unlike previously described immune-evasion genes, inhibited CTLs without blocking class I surface expression, m152 was necessary to block antigen presentation to both Kb- and Db-restricted CTL clones, while m4 was necessary to block presentation only to Kb-restricted clones. m152 caused complete retention of Db, but only partial retention of Kb, in a pre-Golgi compartment. Thus, while m152 effectively inhibited Db-restricted CTLs, m4 was required to completely inhibit Kb-restricted CTLs. We propose that cytomegaloviruses encode multiple immune-evasion genes in order to cope with the diversity of class I molecules in outbred host populations.

Original languageEnglish (US)
Pages (from-to)967-977
Number of pages11
JournalJournal of Experimental Medicine
Volume194
Issue number7
DOIs
StatePublished - Oct 1 2001

Keywords

  • Class I
  • Cytotoxic T lymphocyte
  • Immune evasion
  • MHC
  • Murine cytomegalovirus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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