title: MHC class I cross-presentation by dendritic cells counteracts viral immune evasion.
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.
authors.affiliation: Institute for Immunology, Ludwig-Maximilians-University Munich Munich, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Nopora
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Bernhard
authors.forename: Christine
authors.initials: C
authors.lastname: Ried
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Castello
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.forename: Peggy
authors.initials: P
authors.lastname: Marconi
authors.forename: Ulrich
authors.initials: U
authors.lastname: Koszinowski
authors.forename: Thomas
authors.initials: T
authors.lastname: Brocker