TY - JOUR
T1 - MHC class I cross-presentation by dendritic cells counteracts viral immune evasion
AU - Nopora, Katrin
AU - Bernhard, Caroline A.
AU - Ried, Christine
AU - Castello, Alejandro A.
AU - Murphy, Kenneth M.
AU - Marconi, Peggy
AU - Koszinowski, Ulrich
AU - Brocker, Thomas
PY - 2012
Y1 - 2012
N2 - 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 crosspresentation 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 toT 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.
AB - 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 crosspresentation 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 toT 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.
KW - Cross-priming
KW - Dendritic cells
KW - Immune evasion
UR - http://www.scopus.com/inward/record.url?scp=84874215696&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2012.00348
DO - 10.3389/fimmu.2012.00348
M3 - Article
C2 - 23189079
AN - SCOPUS:84874215696
SN - 1664-3224
VL - 3
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - NOV
M1 - Article 348
ER -