Control of cross‐presentation during dendritic cell maturation

Gil‐Torregrosa, Beatriz C.; Lennon-Duménil, Ana María; Kessler, Benedikt M.; Guermonprez, Pierre; Ploegh, Hidde L.; Fruci, Doriana; Endert, Peter Van; Amigorena, Sébastian

doi:10.1002/eji.200324508

Cited by 135 publications

(165 citation statements)

References 44 publications

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“…Immunoproteasomes, which have been implicated in cross-presentation [23], could also account for GP276 poor cross-presentation since it can downregulate GP276 presentation [24]. We have detected LMP7 expression in DC2.4 (unpublished data), which concurs with the previous data showing that immunoproteasomes are expressed in DC irrespective of their maturation states [25].…”

Section: Discussionsupporting

confidence: 91%

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

et al. 2010

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The initiation of CD8 1 T cell (CTL) immune responses can occur via cross-priming. Recent data suggested a relationship between cross-presentation and immunodominance of epitope-specific T cells. To test this association, we evaluated the efficacy of crosspresentation for several virus epitopes in vitro and examined if this can be extrapolated in vivo. Employing lymphocytic choriomeningitis virus (LCMV), we demonstrate that the cross-presentation and cross-priming of LCMV antigens were dominated by NP396, but not NP205 when analyzing the LCMV-NP. Although with LCMV-GP, cross-presentation was dominated by GP276, and cross-priming was dominated by GP33. Importantly, although NP396 was significantly more efficient than GP33 in cross-presentation, cross-priming of their specific CTL was comparable. In a subsequent virus challenge after cross-priming, GP33-specific CTL dominated the response. Accordingly, based on our data, the ability of viral epitopes to be cross-presented in vitro does not entirely reflect what would occur in cross-priming. Thus, weak cross-presenting antigens may still cross-prime an efficient CTL response depending on other in vivo elements such as the naïve T-cell precursor frequencies.

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Section: Discussionsupporting

confidence: 91%

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

et al. 2010

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“…Immature DCs, as well as DCs matured by using the cytokine mixture, were tested for the presence of both the inhibitory receptor Fc␥RIIb (by using anti-Fc␥RIIb antibody 2B6-FITC, MacroGenics) and the activating Fc␥R Fc␥RIIa (clone IV.3, Medarex, Annandale, NJ). Prior studies have shown that Fc␥RII is the most common Fc␥R expressed on human monocyte-derived DCs (17,20,22,27). However, these studies did not specifically examine the pattern of activating versus inhibitory isoforms of this receptor.…”

Section: Blocking Inhibitory Fc␥rs On Human Monocyte-derived Dcs Andmentioning

confidence: 99%

“…In addition, targeting of antigens to Fc␥Rs on human DCs, including immune complexes and antibody-coated tumor cells, leads to enhanced generation of both CD4 ϩ and CD8 ϩ T cell responses in culture (6, 14-18). Therefore, the targeting of antigens to DCs by means of immune complexes can mediate both maturation of DCs and antigen presentation, leading to immunity that includes cross-presentation of tumors and autoantigens to CD8 ϩ T cells (17,(19)(20)(21)(22)(23).The Fc␥R system represents a balance of activating and inhibitory receptors that determines the outcome of immune complex-mediated inflammation and immunity (24). Prior studies by Kalergis and Ravetch (25) have shown that targeting immune complexes to DCs from mice genetically lacking inhibitory Fc␥RIIb can lead to enhanced generation of antigenspecific CD8 ϩ T cell immunity in vitro and in vivo.…”

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confidence: 99%

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confidence: 99%

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Selective blockade of inhibitory Fcγ receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibody-coated tumor cells

Dhodapkar

Kaufman²,

Ehlers³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

216

212

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The final differentiation or maturation of dendritic cells (DCs) in response to environmental stimuli influences their ability to both initiate immunity and determine the quality of the response to antigens. Circulating immune complexes and cell-bound immunoglobulins present in normal human sera represent a potential stimulus for inadvertent DC activation in the steady state and during autoimmunity. Here, we show that selective blockade of the inhibitory Fc␥ receptor (Fc␥R) Fc␥RIIb with recently developed monoclonal antibodies leads to maturation of human monocytederived DCs, which depends on the presence of IgG in normal human plasma. Plasma, in the presence of an Fc␥RIIb blockade, caused the DCs to up-regulate the expression of costimulatory molecules and to produce the inflammatory mediator IL-12p70. Fc␥RIIb blockade of DCs loaded with tumor cells led to increased tumor-specific T cell immunity without the need for exogenous stimuli other than human plasma. Therefore, the activation status of DCs in the presence of normal human serum depends on the balance between activating and inhibitory Fc␥Rs and can be enhanced by new antibodies that react selectively with Fc␥RIIb. These data suggest an approach for modifying this balance to enhance immunity to immune complexes and antibody-coated tumor cells and to silence DC activation by immune complexes in autoimmune states.autoimmunity ͉ monoclonal antibody ͉ myeloma ͉ vaccination ͉ crosspresentation D endritic cells (DCs) are highly differentiated antigenpresenting cells that play a key role in the initiation and regulation of T cell immunity to pathogens and tumors while at the same time preventing immune responses against self-tissues or environmental antigens (1, 2). A critical property of DCs is that their ability to activate or inhibit immunity is linked to environmental stimuli, which determine their final differentiation or maturation status (3). Several stimuli, such as pathogens recognized by means of Toll-like receptors, CD40L, heat shock proteins, inflammatory cytokines, and innate lymphocytes, can lead to DC maturation and T cell immunity (2). However, under steady state, DCs must avoid inappropriate activation to prevent responses to self-antigens (''horror autotoxicus'') and harmless environmental antigens (4, 5). Specific pathways that prevent spontaneous DC activation are not as well understood as microbial and inflammatory stimuli.Circulating immune complexes and cell-bound immunoglobulins present in normal human sera represent a potential stimulus for DC activation in the steady state (6). The physiologic consequences of cell-bound IgG and immune complexes are modulated by a balance between activating and inhibitory Fc␥ receptors (Fc␥Rs) and include immune regulatory and inflammatory responses (7-10). Engagement of activating Fc␥Rs that contain an immune tyrosine-based activation motif on effector cells, including monocytes, neutrophils, natural killer cells, and mast cells, mediates phagocytosis, antibody-dependent cellmediated cytotoxicity, and r...

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“…Cells were washed several times with RPMI 1640 before being used in vitro or in vivo. In some experiments, soluble OVA protein (screened for the absence of peptide contamination) (10) was introduced into BM-DCs or spleen cells via electroporation, as previously described (18). In other experiments, DCs were infected with a replication-defective recombinant serotype 5 adenovirus vector expressing either a nonsecreted OVA (Ad-OVA) or GFP (Ad-GFP) as a control, at 3000 virus particles (vp) per cell (10,19) for 3 h in medium supplemented with GM-CSF.…”

Section: Antigensmentioning

confidence: 99%

Acquisition of MHC:Peptide Complexes by Dendritic Cells Contributes to the Generation of Antiviral CD8+ T Cell Immunity In Vivo

Smyth

Hervouet

Hayday

et al. 2012

The Journal of Immunology

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There is an increasing body of evidence suggesting that the transfer of preformed MHC class I:peptide complexes between a virus-infected cell and an uninfected APC, termed cross-dressing, represents an important mechanism of Ag presentation to CD8+ T cells in host defense. However, although it has been shown that memory CD8+ T cells can be activated by uninfected dendritic cells (DCs) cross-dressed by Ag from virus-infected parenchymal cells, it is unknown whether conditions exist during virus infection in which naive CD8+ T cells are primed and differentiate to cytolytic effectors through cross-dressing, and indeed which DC subset would be responsible. In this study, we determine whether the transfer of MHC class I:peptide complexes between infected and uninfected murine DC plays a role in CD8+ T cell priming to viral Ags in vivo. We show that MHC class I:peptide complexes from peptide-pulsed or virus-infected DCs are indeed acquired by splenic CD8α− DCs in vivo. Furthermore, the acquired MHC class I:peptide complexes are functional in that they induced Ag-specific CD8+ T cell effectors with cytolytic function. As CD8α− DCs are poor cross-presenters, this may represent the main mechanism by which CD8α− DCs present exogenously encountered Ag to CD8+ T cells. The sharing of Ag as preformed MHC class I:peptide complexes between infected and uninfected DCs without the restraints of Ag processing may have evolved to accurately amplify the response and also engage multiple DC subsets critical in the generation of strong antiviral immunity.

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Control of cross‐presentation during dendritic cell maturation

Cited by 135 publications

References 44 publications

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

The outcome of cross‐priming during virus infection is not directly linked to the ability of the antigen to be cross‐presented

Selective blockade of inhibitory Fcγ receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibody-coated tumor cells

Acquisition of MHC:Peptide Complexes by Dendritic Cells Contributes to the Generation of Antiviral CD8+ T Cell Immunity In Vivo

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