AUTHOR=Nopora Katrin , Bernhard Caroline A., Ried Christine , Castello Alejandro A., Murphy Kenneth M., Marconi Peggy , Koszinowski Ulrich H., Brocker Thomas TITLE=MHC Class I Cross-Presentation by Dendritic Cells Counteracts Viral Immune Evasion JOURNAL=Frontiers in Immunology VOLUME=3 YEAR=2012 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2012.00348 DOI=10.3389/fimmu.2012.00348 ISSN=1664-3224 ABSTRACT=

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 CD8α+ DCs, they were independent of cross-presentation. Therefore HSV-specific CTL-responses entirely depend on the CD8α+ 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.