scholarly journals N-terminal functional region of the invariant chain efficiently targets the binding of a CTL epitope to MHC class I molecules during cross-presentation

2014 ◽  
Vol 13 (2) ◽  
pp. 2438-2450 ◽  
Author(s):  
C. Wu ◽  
D.G. Zhang ◽  
F.F. Chen ◽  
X.L. Liu ◽  
S.J. Liu ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Class I ◽  
Invariant Chain ◽  
Functional Region ◽  
Cross Presentation ◽  
Ctl Epitope ◽  
Mhc Class I Molecules

scholarly journals Long-Peptide Cross-Presentation by Human Dendritic Cells Occurs in Vacuoles by Peptide Exchange on Nascent MHC Class I Molecules

2016 ◽  
Vol 196 (4) ◽  
pp. 1711-1720 ◽  
Author(s):  
Wenbin Ma ◽  
Yi Zhang ◽  
Nathalie Vigneron ◽  
Vincent Stroobant ◽  
Kris Thielemans ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mhc Class I ◽  
Class I ◽  
Cross Presentation ◽  
Peptide Exchange ◽  
Human Dendritic Cells ◽  
Mhc Class I Molecules

hDectin-1 Mediates Cross-Presentation of Epitopes Via the Cytosolic Pathway.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2313-2313
Author(s):  
Frank Grünebach ◽  
Markus M. Weck ◽  
Silke Appel ◽  
Daniela Werth ◽  
Christian Sinzger ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Brefeldin A ◽  
Hla Class I ◽  
Class I ◽  
Apoptotic Cells ◽  
Down Regulation ◽  
Cross Presentation ◽  
Hla Class I Molecules ◽  
The Cross ◽  
Mhc Class I Molecules

Abstract Human (h)Dectin-1 is a member of the C-type-lectin-like receptor family that was shown to be the major receptor for fungal β-glucans and to play an important role in cellular responses mediated by these carbohydrates. It is mainly expressed on human DCs and macrophages. In our study, we observed that activation of monocyte-derived dendritic cells (MDCs) with TLR3 ligand (poly I:C) but not with TLR ligand 7/8 (R848) resulted in down-regulation of hDectin-1 expression and this down-regulation correlated with a reduced uptake of apoptotic cells in phagocytosis assays. In order to analyze the possible cross-presentation of engulfed antigens we used CMV infected human fibroblasts (HFF). We found that hDectin-1 is involved in the uptake of CMV-infected HFF leading to cross-presentation of CMV-derived peptides on MHC class I molecules and activation of CMV pp65-specific CD8+ T-lymphocytes. To further delineate the pathway leading to presentation, we pretreated MDCs with compounds that inhibit processing of antigens at defined steps during presentation. Cytosolic protein degradation is performed by the proteasome, a large multicatalytic protease complex. Lactacystin specifically inhibits the 20S and 26S proteasome activity by targeting the catalytic subunit. In standard 51Cr-release assays, addition of lactacystin completely inhibited the presentation of pp65-derived peptides indicating the involvement of the proteasome in these process. The fungal product brefeldin A blocks the MHC class I processing pathway by specifically inhibiting the vesicular egress from the ER and the Golgi complex. In line with previous findings, incubation with brefeldin A almost completely abolished the lysis of MDCs incubated with CMV+ HFF. To further analyze whether the cross-presentation of CMV-derived peptides on HLA class I molecules was dependent on lysosomal proteases, MDCs that were co-incubated with HFF as above were treated with the lysosomotropic agent chloroquine that prevents acidification of the lysosomal compartment involved in the exogenous pathway of antigen presentation. The addition of chloroquine had no effect on the cross-presentation of CMV-derived epitopes on HLA class I-molecules. Summarized, the data reported here show that hDectin-1 functions not only as a pattern recognition receptor in innate immunity but is also involved in the clearing of apoptotic cells and cross-presentation of cellular antigens on MHC class I molecules to specific CTLs.

scholarly journals Constitutive versus Activation-dependent Cross-Presentation of Immune Complexes by CD8+ and CD8− Dendritic Cells In Vivo

2002 ◽  
Vol 196 (6) ◽  
pp. 817-827 ◽  
Author(s):  
Joke M.M. den Haan ◽  
Michael J. Bevan
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Mhc Class I ◽  
Cd8 T Cells ◽  
Immune Complexes ◽  
Class I ◽  
Cross Presentation ◽  
Deficient Mice ◽  
Mhc Class I Molecules

Murine splenic dendritic cells (DCs) can be divided into two subsets based on CD8α expression, but the specific role of each subset in stimulation of T cells is largely unknown. An important function of DCs is the ability to take up exogenous antigens and cross-present them in the context of major histocompatibility complex (MHC) class I molecules to CD8+ T cells. We previously demonstrated that, when cell-associated ovalbumin (OVA) is injected into mice, only the CD8+ DC subset cross-presents OVA in the context of MHC class I. In contrast to this selectivity with cell-associated antigen, we show here that both DC subsets isolated from mice injected with OVA/anti-OVA immune complexes (OVA-IC) cross-present OVA to CD8+ T cells. The use of immunoglobulin G Fc receptor (FcγR) common γ-chain–deficient mice revealed that the cross-presentation by CD8− DCs depended on the expression of γ-chain–containing activating FcγRs, whereas cross-presentation by CD8+ DCs was not reduced in γ-chain–deficient mice. These results suggest that although CD8+ DCs constitutively cross-present exogenous antigens in the context of MHC class I molecules, CD8− DCs only do so after activation, such as via ligation of FcγRs. Cross-presentation of immune complexes may play an important role in autoimmune diseases and the therapeutic effect of antitumor antibodies.

Allele-dependent association of chicken MHC class I molecules with the invariant chain

2014 ◽  
Vol 160 (3-4) ◽  
pp. 273-280 ◽  
Author(s):  
Fangfang Chen ◽  
Ling Pan ◽  
Jiegui Zhang ◽  
Xiuhong Zhou ◽  
Juan Li ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Class I ◽  
Invariant Chain ◽  
Mhc Class I Molecules ◽  
Chicken Mhc

scholarly journals The GTPase Rab3b/3c-positive recycling vesicles are involved in cross-presentation in dendritic cells

2009 ◽  
Vol 106 (37) ◽  
pp. 15801-15806 ◽  
Author(s):  
Liyun Zou ◽  
Jingran Zhou ◽  
Jinyu Zhang ◽  
Jingyi Li ◽  
Na Liu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Mhc Class I ◽  
Membrane Trafficking ◽  
Molecular Mechanisms ◽  
Class I ◽  
Recycling Rate ◽  
Rab Gtpases ◽  
Cross Presentation ◽  
Intracellular Membrane Transport ◽  
Mhc Class I Molecules

Antigen cross-presentation in dendritic cells is a complex intracellular membrane transport process, but the underlying molecular mechanisms remain to be thoroughly investigated. In this study, we examined the effect of siRNA-mediated knockdown of 57 Rab GTPases, the key regulators of membrane trafficking, on antigen cross-presentation. Twelve Rab GTPases were identified to be associated with antigen cross-presentation, and Rab3b/3c was indicated to be colocalized with MHC class I molecules at perinuclear tubular structure. Tracing with fluorescence protein-tagged β2-microglobulin demonstrated that the MHC class I molecules were internalized from the plasma membrane to Rab3b/3c-positive compartments, which were also colocalized with the internalized transferrin. Moreover, depletion of Rab3b/3c strongly reduced the fast phase recycling rate of transferrin receptors. Furthermore, the Rab3b/3c-positive compartments were colocalized with a fraction of Rab27a at a juxtaposition of phagosomes. Together, these data demonstrate that Rab3b/3c-positive recycling vesicles are involved in and may constitute one of the recycling compartments in exogenous antigen cross-presentation.

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