Frontiers in Immunology (Nov 2012)

MHC class I cross-presentation by Dendritic Cells counteracts viral immune evasion

  • Katrin eNopora,
  • Caroline Andree Bernhard,
  • Christine eRied,
  • Alejandro A Castello,
  • Alejandro A Castello,
  • Kenneth M Murphy,
  • Peggy eMarconi,
  • Ulrich Helmut Koszinowski,
  • Thomas eBrocker

DOI
https://doi.org/10.3389/fimmu.2012.00348
Journal volume & issue
Vol. 3

Abstract

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DCs very potently activate CD8+ T cells specific for viral peptides bound to MHC class I molecules. However, many viruses have evolved immune evasion mechanisms, which inactivate infected DCs and might reduce priming of T cells. Then MHC class I cross-presentation of exogenous viral Ag by non-infected DCs may become crucial to assure CD8+ T cell responses. Although many vital functions of infected DCs are inhibited in vitro by many different viruses, the contributions of cross-presentation to T cell immunity when confronted with viral immune inactivation in vivo has not been demonstrated up to now, and remains controversial. Here we show that priming of Herpes Simplex Virus (HSV)-, but not murine cytomegalovirus (mCMV)-specific CD8+ T cells was severely reduced in mice with a DC-specific cross-presentation deficiency. In contrast, while CD8+ T cell responses to mutant HSV, which lacks crucial inhibitory genes, also depended on CD8+ DCs, they were independent of cross-presentation. Therefore HSV-specific CTL-responses entirely depend on the CD8+ DC-subset, which present via direct or cross-presentation mechanisms depending on the immune-evasion equipment of virus. Our data establish the contribution of cross-presentation to counteract viral immune evasion mechanisms in some, but not all viruses.

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