Evidence for a role of ganglioside GM1 in antigen presentation: binding enhances presentation of Escherichia coli enterotoxin B subunit (EtxB) to CD4+ T cells

Nashar, Toufic O.; Betteridge, Zoë; Mitchell, Richard N.

doi:10.1093/intimm/13.4.541

Cited by 40 publications

(47 citation statements)

References 55 publications

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“…Consistent with this idea, lipid rafts and actin cytoskeleton have been implicated in receptor clearance (8 -11, 23). In addition, previous studies have shown that clathrin-mediated internalization is not solely responsible for the clearance of receptors from the cell surface (31)(32)(33)(34). However, this does not refute the importance of clathrin-mediated endocytosis, because productive processing of Ag internalized in the absence of kinase activation is unlikely.…”

Section: Discussionmentioning

confidence: 82%

Independent Trafficking of Ig-α/Ig-β and μ-Heavy Chain Is Facilitated by Dissociation of the B Cell Antigen Receptor Complex

Kim

Cramer

Mueller

et al. 2005

The Journal of Immunology

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The BCR relays extracellular signals and internalizes Ag for processing and presentation. We have previously demonstrated that ligation of the BCR destabilizes Ig-α/Ig-β (Ig-αβ) from μ-H chain (μm). In this study we report that receptor destabilization represents a physical separation of μm from Ig-αβ. Sucrose gradient fractionation localized Ig-αβ to GM1-containing lipid microdomains in the absence of μm. Confocal and electron microscopy studies revealed the colocalization of unsheathed μm with clathrin-coated vesicles. Furthermore, μm failed to associate with clathrin-coated vesicles when receptor destabilization was inhibited, suggesting that unsheathing of μm is required for clathrin-mediated endocytosis. In summary, we found that Ag stimulation physically separates Ig-αβ from μm, facilitating concomitant signal transduction and Ag delivery to the endocytic compartment.

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Section: Discussionmentioning

confidence: 82%

Independent Trafficking of Ig-α/Ig-β and μ-Heavy Chain Is Facilitated by Dissociation of the B Cell Antigen Receptor Complex

Kim

Cramer

Mueller

et al. 2005

The Journal of Immunology

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“…In regard to the other microbial toxins, it has been reported that Shiga toxin B subunit fused to tumor peptide elicits antitumor immune response to P815 murine mastocytoma (10). Molecular mechanism of adjuvant property of rCTB is not understood completely although binding to GM 1 gangliosides is required for rCTB to act as an adjuvant (21). Like other bacterial components, rCTB stimulates immune system by inducing maturation of APC (8).…”

Section: Discussionmentioning

confidence: 99%

Recombinant Cholera Toxin B Subunit Activates Dendritic Cells and Enhances Antitumor Immunity

Isomura

Yasuda

Tsujimura

et al. 2005

Microbiology and Immunology

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Activation of dendritic cells (DC) is crucial for priming of cytotoxic T lymphocytes (CTL), which have a critical role in tumor immunity, and it is considered that adjuvants are necessary for activation of DC and for enhancement of cellular immunity. In this study, we examined an adjuvant capacity of recombinant cholera toxin B subunit (rCTB), which is non‐toxic subunit of cholera toxin, on maturation of murine splenic DC. After the in vitro incubation of DC with rCTB, the expression of MHC class II and B7–2 on DC was upregulated and the secretion of IL‐12 from DC was enhanced. In addition, larger DC with longer dendrites were observed. These data suggest that rCTB induced DC maturation. Subsequently, we examined the induction of tumor immunity by rCTB‐treated DC by employing Meth A tumor cells in mice. Pretreatment with subcutaneous injection of rCTB‐treated DC pulsed with Meth A tumor lysate inhibited the growth of the tumor cells depending on the number of DC. Moreover, intratumoral injection of rCTB‐treated DC pulsed with tumor lysate had therapeutic effect against established Meth A tumor. Immunization with DC activated by rCTB and the tumor lysate increased number of CTL precursor recognizing Meth A tumor. The antitumor immune response was significantly inhibited in CD8+ T cell‐depleted mice, although substantial antitumor effect was observed in CD4+ T cell‐depleted mice. These results indicated that rCTB acts as an adjuvant to enhance antitumor immunity through DC maturation and that CD8+ T cells play a dominant role in the tumor immunity. Being considered to be safe, rCTB may be useful as an effective adjuvant to raise immunity for a tumor in clinical application.

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“…There have been studies of the effects of CT on APC; however, the mechanism underlying the induction of this activity remains to be precisely elucidated. For example, it was shown that CT, but not CT-B, up-regulates the expression of the costimulatory molecule B7-2, but not B7-1, on murine M ¶ and B cells [9][10][11][12]. In humans, CT induced up-regulation of both B7-1 and B7-2 in blood monocyte-derived DC.…”

Section: Introductionmentioning

confidence: 99%

Cholera toxin activates dendritic cells through dependence on GM1‐ganglioside which is mediated by NF‐κB translocation

et al. 2003

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Cholera toxin (CT) is a potent adjuvant; however, the mechanism for its ability to enhance mucosal immunity has not been fully elucidated. We report here that CT exerts its adjuvant properties by signaling through the GM1 ganglioside receptor. When ganglioside-defective mice were given the antigen (Ag) ovalbumin (OVA) with CT by the oral route, CT failed to support either OVA-specific antibody or CD4 + T cell responses. In vitro treatment of murine bone marrow-derived dendritic cells (DC) with CT induced full maturation as evidenced by upregulation of the costimulatory molecules, as well as by an enhanced ability to effectively present OVA for Ag-specific T cell responses. On the other hand, ganglioside-defective DC failed to differentiate to full function as Ag-presenting cells in response to CT. Since ganglioside-defective DC showed a mature phenotype after stimulation with lipopolysaccharide (LPS), the effects of CT on DC was independent of signal transduction through adjuvant receptor for LPS, the Toll-like receptor 4. Furthermore, CT also induced nuclear translocation of nuclear factor (NF)-‹ B in DC in a GM1-dependent fashion. These results highlight gangliosides expressed by DC for recognition of the non-self protein bacterial enterotoxin, which employ a unique signaling pathway to induce both innate and adaptive immunity.

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Evidence for a role of ganglioside GM1 in antigen presentation: binding enhances presentation of Escherichia coli enterotoxin B subunit (EtxB) to CD4+ T cells

Cited by 40 publications

References 55 publications

Independent Trafficking of Ig-α/Ig-β and μ-Heavy Chain Is Facilitated by Dissociation of the B Cell Antigen Receptor Complex

Independent Trafficking of Ig-α/Ig-β and μ-Heavy Chain Is Facilitated by Dissociation of the B Cell Antigen Receptor Complex

Recombinant Cholera Toxin B Subunit Activates Dendritic Cells and Enhances Antitumor Immunity

Cholera toxin activates dendritic cells through dependence on GM1‐ganglioside which is mediated by NF‐κB translocation

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