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

Frontiers in Immunology

Kenneth M Murphy¹  Ulrich Helmut Koszinowski²  Christine eRied²  Caroline Andree Bernhard²  Katrin eNopora²  Thomas eBrocker²  Alejandro A Castello³  Peggy eMarconi⁴ 

[1] Howard Hughes Medical Institute;Ludwig-Maximilians-University Munich;Universidad Nacional de Quilmes;University of Ferrara;

关键词: Antigen Presentation;    Cross-Priming;    Dendritic Cells;    Immune Evasion;    Virus infection;   

DOI  :  10.3389/fimmu.2012.00348

来源: DOAJ

【 摘 要 】

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)-specificCD8+ 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.

【 授权许可】

Unknown