Induction of MHC Class I Presentation of Exogenous Antigen by Dendritic Cells Is Controlled by CD4+ T Cells Engaging Class II Molecules in Cholesterol-Rich Domains

Machy, Patrick; Serre, Karine; Baillet, Marion; Leserman, Lee

doi:10.4049/jimmunol.168.3.1172

Cited by 46 publications

(42 citation statements)

References 50 publications

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“…In this context, the spore peptidoglycan cortex, with a unique muramic delta-lactam structural modification and the spore DNA are possible targets for PRR. A further explanation may lie in the fact that primed CD4 + T cells can license DC to cross-prime exogenous antigen through prolonged engagement and mutual stimulation through CD86 and CD40L [45] and macropinocytosis [46]. In support, we observed that B. subtilis spores induced a strong, IFN-c-dominated CD4 T cell response to exogenous spore proteins.…”

Section: Discussionsupporting

confidence: 73%

Bacillus subtilis spores: A novel microparticle adjuvant which can instruct a balanced Th1 and Th2 immune response to specific antigen

et al. 2007

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There is a current need for safe, cheap, and effective vaccine adjuvants, to combine with sub-unit antigens to enhance their immunogenicity. In this study we have used probiotic Bacillus subtilis spores, known to be safe and fully tolerated by ingestion in man, and explored their ability to influence the magnitude and diversity of immune responses induced against two model antigens, tetanus toxoid fragment C (TT) and ovalbumin (OVA) in mice. The results show that B. subtilis spores not only increased antibody and T cell responses to a co-administered soluble antigen, but also broadened them, to include both antigen-specific CD4 + and CD8 + T cell responses as well as complement and non-complement fixing antibody isotypes. Furthermore, following intranasal immunization, spores augmented specific IgA to co-administered antigen both in the local respiratory and distal vaginal mucosa, as well as increased antigen-specific IgG antibody in draining LN and blood. Collectively, these data demonstrate that naturally occurring, non-pathogenic, non-commensal spores of B. subtilis both instruct and augment polyvalent immune responses and highlight their clinical potential in future vaccines to generate broad-based immunity.

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Section: Discussionsupporting

confidence: 73%

Bacillus subtilis spores: A novel microparticle adjuvant which can instruct a balanced Th1 and Th2 immune response to specific antigen

et al. 2007

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“…Recently, DC rafts have been shown to contain a subset of MHC class II-peptide complexes (24). Signals transmitted via DC rafts were shown to condition the DC for the activation of CD8 ϩ T cells (25). It is tempting to speculate that small GTPases likewise regulate the export of lipid rafts and of their components to the DC surface and thereby control phenotype and function of DCs.…”

Section: Endritic Cells (Dcs)mentioning

confidence: 99%

Lipid Raft-Associated GTPase Signaling Controls Morphology and CD8+ T Cell Stimulatory Capacity of Human Dendritic Cells

Jaksits

Bauer

Kriehuber

et al. 2004

The Journal of Immunology

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Their eponymous morphology and unique ability to activate naive T cells are hallmark features of dendritic cells (DCs). Specific properties of the actin cytoskeleton may define both characteristics. In search for regulators that coordinate DC phenotype and function, we observed strongly increased expression of the actin-remodeling GTPases Cdc42 and Rac1 during DC development from human stem cells. Cdc42 and Rac1 are constitutively active in immature DCs, and their activity is further up-regulated by maturational stimuli such as LPS or CD40L. Activation of Rac1 is associated with its rapid recruitment into lipid rafts. Cdc42 is not recruited into rafts, but readily activated by raft-associated moieties. The functional interplay of rafts, GTPases, and cortical actin is further shown by GTPase activation and actin remodeling after pharmacological disruption of lipid rafts and by the loss of the actin-based DC morphology by transfection of dominant-negative Cdc42 and Rac1. Both Cdc42 and Rac1 also control the transport of essential immunostimulatory molecules to the DC surface. Transfection with dominant-negative GTPases led to reduced surface expression of MHC class I and CD86. Consecutively, DCs display a reduced stimulatory capacity for CD8+ T cells, whereas MHC class II-dependent stimulation of CD4+ T cells remains unperturbed. We conclude that Cdc42 and Rac1 signaling controls DC morphology and conditions DCs for efficient CD8+ T cell stimulation.

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“…We, therefore, conducted experiments with LK-35.2 cells treated with anti-CD40 for varying lengths of time and fixed with paraformaldehyde before the addition of synthetic peptides. CD40 ligation enhanced the ability of APC to stimulate IL-2 release by T cell hybridomas specific for HEL 34 -45 or bovine RNase A [43][44][45][46][47][48][49][50][51][52][53][54][55][56] as early as 30 min after the addition of anti-CD40 (Fig. 2B, center and right).…”

Section: Cd40 Ligation-induced Enhancement Of the Ability Of Apc To Amentioning

confidence: 99%

CD40-Induced Aggregation of MHC Class II and CD80 on the Cell Surface Leads to an Early Enhancement in Antigen Presentation

Clatza

Bonifaz

Vignali

et al. 2003

The Journal of Immunology

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Ligation of CD40 on B cells increases their ability to present Ag and to activate MHC class II (MHC-II)-restricted T cells. How this occurs is not entirely clear. In this study we demonstrate that CD40 ligation on Ag-presenting B cells (APC) for a short period between 30 min and 3 h has a rapid, augmenting effect on the ability of a B cell line and normal B cells to activate T cells. This is not due to alterations in Ag processing or to an increase in surface expression of CD80, CD86, ICAM-1, or MHC-II. This effect is particularly evident with naive, resting T lymphocytes and appears to be more pronounced under limiting Ag concentrations. Shortly after CD40 ligation on a B cell line, MHC-II and CD80 progressively accumulated in cholesterol-enriched microdomains on the cell surface, which correlated with an initial enhancement in their Ag presentation ability. Moreover, CD40 ligation induced a second, late, more sustained enhancement of Ag presentation, which correlates with a significant increase in CD80 expression by APC. Thus, CD40 signaling enhances the efficiency with which APC activate T cells by at least two related, but distinct, mechanisms: an early stage characterized by aggregation of MHC-II and CD80 clusters, and a late stage in which a significant increase in CD80 expression is observed. These results raise the possibility that one important role of CD40 is to contribute to the formation of the immunological synapse on the APC side.

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Induction of MHC Class I Presentation of Exogenous Antigen by Dendritic Cells Is Controlled by CD4+ T Cells Engaging Class II Molecules in Cholesterol-Rich Domains

Cited by 46 publications

References 50 publications

Bacillus subtilis spores: A novel microparticle adjuvant which can instruct a balanced Th1 and Th2 immune response to specific antigen

Bacillus subtilis spores: A novel microparticle adjuvant which can instruct a balanced Th1 and Th2 immune response to specific antigen

Lipid Raft-Associated GTPase Signaling Controls Morphology and CD8+ T Cell Stimulatory Capacity of Human Dendritic Cells

CD40-Induced Aggregation of MHC Class II and CD80 on the Cell Surface Leads to an Early Enhancement in Antigen Presentation

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