Cross-presentation of a spread-defective MCMV is sufficient to prime the majority of virus-specific CD8+ T cells

Christopher M. Snyder, Jane E. Allan, Elizabeth L. Bonnett, Carmen M. Doom, Ann Hill

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

CD8+ T cells can be primed by peptides derived from endogenous proteins (direct presentation), or exogenously acquired protein (cross-presentation). However, the relative ability of these two pathways to prime CD8+ T cells during a viral infection remains controversial. Cytomegaloviruses (CMVs) can infect professional antigen presenting cells (APCs), including dendritic cells, thus providing peptides for direct presentation. However, the viral immune evasion genes profoundly impair recognition of infected cells by CD8+ T cells. Nevertheless, CMV infection elicits a very strong CD8+ T cell response, prompting its recent use as a vaccine vector. We have shown previously that deleting the immune evasion genes from murine cytomegalovirus (MCMV) that target class I MHC presentation, has no impact on the size or breadth of the CD8+ T cell response elicited by infection, suggesting that the majority of MCMV-specific CD8+ T cells in vivo are not directly primed by infected professional APCs. Here we use a novel spread-defective mutant of MCMV, lacking the essential glycoprotein gL, to show that cross-presentation alone can account for the majority of MCMV-specific CD8+ T cell responses to the virus. Our data support the conclusion that cross-presentation is the primary mode of antigen presentation by which CD8+ T cells are primed during MCMV infection.

Original languageEnglish (US)
Article numbere9681
JournalPLoS One
Volume5
Issue number3
DOIs
StatePublished - Mar 12 2010

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Cross-Priming
Muromegalovirus
Cytomegalovirus
T-cells
Viruses
T-lymphocytes
T-Lymphocytes
viruses
mice
immune evasion
Immune Evasion
antigen-presenting cells
Cytomegalovirus Infections
Antigen-Presenting Cells
Genes
peptides
vector vaccines
antigen presentation
Peptides
Antigen Presentation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cross-presentation of a spread-defective MCMV is sufficient to prime the majority of virus-specific CD8+ T cells. / Snyder, Christopher M.; Allan, Jane E.; Bonnett, Elizabeth L.; Doom, Carmen M.; Hill, Ann.

In: PLoS One, Vol. 5, No. 3, e9681, 12.03.2010.

Research output: Contribution to journalArticle

Snyder, Christopher M. ; Allan, Jane E. ; Bonnett, Elizabeth L. ; Doom, Carmen M. ; Hill, Ann. / Cross-presentation of a spread-defective MCMV is sufficient to prime the majority of virus-specific CD8+ T cells. In: PLoS One. 2010 ; Vol. 5, No. 3.
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