Distinct effects of recombinant cholera toxin B subunit and holotoxin on different stages of class II MHC antigen processing and presentation by macrophages.

Cholera toxin (CT) is a potent mucosal adjuvant with enhancing effects on Ag presentation, although the mechanisms of its adjuvanticity remain poorly understood. Using an in vitro Ag presentation assay, we found CT and recombinant B subunit (rCTB) to have distinct effects on different stages of processing and class II MHC (MHC-II)-restricted presentation of hen egg lysozyme (HEL). CT treatment of macrophages resulted in enhanced presentation of soluble HEL(48-61) peptide to3A9 hybridoma cells. However, CT had inhibitory effects on intracellular processing of soluble native Ag. Thus, CT inhibited presentation when added prior to HEL, whereas presentation was enhanced when CT was added after HEL exposure and the generation of peptide-MHC-II complexes. Pretreatment of macrophages with CT also markedly inhibited phagocytic processing of a Crl-HEL fusion protein (containing the HEL(48-61) epitope) expressed in intact bacteria (Escherichia coli HB101.Crl-HEL or Salmonella typhimurium 14028s.Crl-HEL), whereas addition of CT to macrophages after a 2-h incubation with the bacteria again enhanced presentation. CT produced little effect on overall uptake and catabolism of radiolabeled HEL or HB101.Crl-HEL. In contrast to the holotoxin, purified rCTB subunit did not inhibit intracellular processing of soluble or bacterial Ag, although it similarly enhanced the presentation of surface HEL-(48-61)-I-Ak complexes to 3A9 cells. These data suggest that the inhibitory effects of CT on Ag processing are mediated by the A subunit.

• Publication year

  1996

• Venue

  Journal of Immunology

• Publication date

  1996-06-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.4049/jimmunol.156.11.4137PMID 8666780
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Oral immunization with recombinant Helicobacter pylori urease induces secretory IgA antibodies and protects mice from challenge with Helicobacter felis.

  1995cited by this paper
• Mutants of Escherichia coli heat-labile toxin lacking ADP-ribosyltransferase activity act as nontoxic, mucosal adjuvants.

  1995cited by this paper
• Dissociation of Escherichia coli heat-labile enterotoxin adjuvanticity from ADP-ribosyltransferase activity

  1995cited by this paper
• Immunization of BALB/c mice against Helicobacter felis infection with Helicobacter pylori urease.

  1994cited by this paper
• Comparison of systemic and mucosal priming for mucosal immune responses to a bacterial protein antigen given with or coupled to cholera toxin (CT) B subunit, and effects of pre-existing anti-CT immunity.

  1994cited by this paper
• Synergistic action of cholera toxin B subunit (and Escherichia coli heat-labile toxin B subunit) and a trace amount of cholera whole toxin as an adjuvant for nasal influenza vaccine.

  1994cited by this paper
• Cholera toxin acts as a potent adjuvant for the induction of cytotoxic T-lymphocyte responses with non-replicating antigens.

  1994cited by this paper
• Parameters that influence the efficiency of processing antigenic epitopes expressed in Salmonella typhimurium

  1994cited by this paper
• Role of trypsin-like cleavage at arginine 192 in the enzymatic and cytotonic activities of Escherichia coli heat-labile enterotoxin

  1994cited by this paper
• Successful immunization against gastric infection with Helicobacter species: use of a cholera toxin B-subunit-whole-cell vaccine

  1994cited by this paper
• Induction of mucosal immunity by intranasal application of a streptococcal surface protein antigen with the cholera toxin B subunit

  1993cited by this paper
• Immunisation against gastric infection with Helicobacter species: first step in the prophylaxis of gastric cancer?

  1993cited by this paper
• Killed Campylobacter elicits immune response and protection when administered with an oral adjuvant.

  1993cited by this paper
• Cholera Toxin Enhances Alloantigen Presentation by Cultured Intestinal Epithelial Cells

  1993cited by this paper
• Cholera toxin adjuvant greatly promotes antigen priming of T cells

  1993cited by this paper
• Protection of germ-free mice from infection by Helicobacter felis after active oral or passive IgA immunization.

  1993cited by this paper
• Protective salivary immunoglobulin A responses against Streptococcus mutans infection after intranasal immunization with S. mutans antigen I/II coupled to the B subunit of cholera toxin

  1993cited by this paper
• Cholera toxin and cholera B subunit as oral-mucosal adjuvant and antigen vector systems.

  1993cited by this paper
• Inhibition of murine T cell activation by cholera toxin B subunit is not mediated through the phosphatidylinositol second messenger system.

  1993cited by this paper
• Recombinant Escherichia coli express a defined, cytoplasmic epitope that is efficiently processed in macrophage phagolysosomes for class II MHC presentation to T lymphocytes.

  1992cited by this paper
• The adjuvant effect of Vibrio cholerae and Escherichia coli heat‐labile enterotoxins is linked to their ADP‐ribosyltransferase activity

  1992cited by this paper
• Cholera toxin adjuvant promotes long-term immunological memory in the gut mucosa to unrelated immunogens after oral immunization.

  1992cited by this paper
• Vaccination by cholera toxin conjugated to a herpes simplex virus type 2 glycoprotein D peptide.

  1992cited by this paper
• Cholera toxin stimulates IL-1 production and enhances antigen presentation by macrophages in vitro.

  1991cited by this paper
• Site-specific mutagenesis of the catalytic subunit of cholera toxin: substituting lysine for arginine 7 causes loss of activity

  1991cited by this paper
• The Adjuvant Action of Cholera Toxin is Associated with an Increased Intestinal Permeability for Luminal Antigens

  1991cited by this paper
• Effects of cholera toxin on human B cells. Cholera toxin induces B cell surface DR expression while it inhibits anti-mu antibody-induced cell proliferation.

  1990cited by this paper
• Cholera holotoxin and its B subunit enhance Peyer's patch B cell responses induced by orally administered influenza virus: Disproportionate cholera toxin enhancement of the IgA B cell response

  1990cited by this paper
• cAMP-independent effects of cholera toxin on B cell activation. I. A possible role for cell surface ganglioside GM1 in B cell activation.

  1990cited by this paper
• Cross-protection against influenza B type virus infection by intranasal inoculation of the HA vaccines combined with cholera toxin B subunit.

  1990cited by this paper
• Cautionary note on the use of the B subunit of cholera toxin as a ganglioside GM1 probe: Detection of cholera toxin A subunit in B subunit preparations by a sensitive adenylate cyclase assay

  1990cited by this paper
• Activation of the cAMP cascade inhibits an early event involved in murine macrophage Ia expression.

  1990cited by this paper
• Whole Cholera Toxin and B Subunit Act Synergistically as an Adjuvant for the Mucosal Immune Response of Mice to Keyhole Limpet Haemocyanin

  1990cited by this paper
• Oral administration of a streptococcal antigen coupled to cholera toxin B subunit evokes strong antibody responses in salivary glands and extramucosal tissues

  1989cited by this paper
• Antigen processing and intracellular Ia. Possible roles of endocytosis and protein synthesis in Ia function.

  1989cited by this paper
• Cholera toxin inhibits resting human T cell activation via a cAMP-independent pathway.

  1989cited by this paper
• Recombinant system for overexpression of cholera toxin B subunit in Vibrio cholerae as a basis for vaccine development.

  1989cited by this paper
• Effectiveness of cholera toxin B subunit as an adjuvant for nasal influenza vaccination despite pre-existing immunity to CTB.

  1989cited by this paper
• Cellular basis of immunomodulation by cholera toxin in vitro with possible association to the adjuvant function in vivo.

  1989cited by this paper
• Fibronectin binding mediated by a novel class of surface organelles on Escherichia coll

  1989cited by this paper
• Adjuvant activity of Escherichia coli heat-labile enterotoxin and effect on the induction of oral tolerance in mice to unrelated protein antigens.

  1988cited by this paper
• Oral administration of cholera toxin-Sendai virus conjugate potentiates gut and respiratory immunity against Sendai virus.

  1988cited by this paper
• Protection against influenza virus infection by vaccine inoculated intranasally with cholera toxin B subunit.

  1988cited by this paper
• Combined oral/nasal immunization protects mice from Sendai virus infection.

  1987cited by this paper
• Inhibition of murine lymphocyte proliferation by the B subunit of cholera toxin.

  1987cited by this paper
• Strong adjuvant properties of cholera toxin on gut mucosal immune responses to orally presented antigens.

  1986cited by this paper
• Cholera toxin inhibits the T-cell antigen receptor-mediated increases in inositol trisphosphate and cytoplasmic free calcium.

  1986cited by this paper
• Generalized systemic and mucosal immunity in mice after mucosal stimulation with cholera toxin.

  1984cited by this paper
• The handling of Listeria monocytogenes by macrophages: the search for an immunogenic molecule in antigen presentation.

  1984cited by this paper
• Cholera toxin B subunit as a carrier protein to stimulate a mucosal immune response.

  1984cited by this paper
• Processing of lysozyme by macrophages: identification of the determinant recognized by two T-cell hybridomas.

  1984cited by this paper
• Actions of cholera toxin and the prevention and treatment of cholera

  1981cited by this paper
• Dissociation and recombination of the subunits of the cholera enterotoxin (choleragen).

  1974cited by this paper

• Immunomodulatory regulation by heat-labile enterotoxins and potential therapeutic applications

  2021cites this paper
• The double adjuvants LTB and CpG significantly enhanced the immuno‐protective effects of recombinant GIT derived from Staphylococcus aureus and Streptococcus in mice

  2018cites this paper
• Bordetella Adenylate Cyclase Toxin Differentially Modulates Toll-Like Receptor-Stimulated Activation, Migration and T Cell Stimulatory Capacity of Dendritic Cells

  2014cites this paper
• Toxins of Vibrio cholerae and Their Role in Inflammation, Pathogenesis, and Immunomodulation

  2011cites this paper
• EFEITO DA SÍLICA NANOESTRUTURADA SBA-15 NA APRESENTAÇÃO ANTIGÊNICA E NA RESPOSTA IMUNE

  2010cites this paper
• Cholera Toxin Impairs the Differentiation of Monocytes into Dendritic Cells, Inducing Professional Antigen-Presenting Myeloid Cells

  2010cites this paper
• Bacterial toxins as immunomodulators.

  2009cites this paper
• Immunomodulation of Gut-Associated Lymphoid Tissue: Current Perspectives

  2009cites this paper
• Identification d'espèces moléculaires de lysophosphatidylcholine présentant des activités adjuvantes en vue d'un développement clinique

  2009cites this paper
• Construction and preclinical evaluation of recombinant Peru-15 expressing high levels of the cholera toxin B subunit as a vaccine against enterotoxigenic Escherichia coli.

  2007cites this paper
• Cholera toxin, LT-I, LT-IIa and LT-IIb: the critical role of ganglioside binding in immunomodulation by Type I and Type II heat-labile enterotoxins

  2007cites this paper
• Lipid Rafts Activation of a Neutral Sphingomyelinase in T Cells by + and Proliferation of Human CD 4 Cholera Toxin B-Subunit Prevents Activation

  2005cites this paper
• Cholera Toxin B-Subunit Prevents Activation and Proliferation of Human CD4+ T Cells by Activation of a Neutral Sphingomyelinase in Lipid Rafts1

  2005cites this paper
• Bacterial toxins: potential weapons against HIV infection.

  2005cites this paper
• Immunomodulation with Enterotoxins for the Generation of Secretory Immunity or Tolerance: Applications for Oral Infections

  2005influential citation
• Mucosal adjuvants.

  2005cites this paper
• Chapter 54 – Mucosal Adjuvants

  2005cites this paper
• Modulation of the immune response by the cholera-like enterotoxins.

  2004cites this paper
• Clostridium difficile Toxin A Carboxyl-Terminus Peptide Lacking ADP-Ribosyltransferase Activity Acts as a Mucosal Adjuvant

  2004cites this paper
• Mucosal Adjuvant ADP-Ribosyltransferase Activity Acts as a Carboxyl-Terminus Peptide Lacking Toxin A Clostridium difficile

  2004cites this paper
• Bacterial Evasion of Host Immune Responses: Enterotoxins: Adjuvants and immune inhibitors

  2003cites this paper
• Cholera toxin activates dendritic cells through dependence on GM1‐ganglioside which is mediated by NF‐κB translocation

  2003cites this paper
• Nasally administered cholera toxin A-subunit acts as a mucosal adjuvant.

  2003cites this paper
• Interaction of bacteria with antigen presenting cells: influences on antigen presentation and antibacterial immunity.

  2003cites this paper
• Mucosal Vaccination Against Encapsulated Respiratory Bacteria – New Potentials for Conjugate Vaccines?

  2003cites this paper
• Mutant Escherichia coli Heat-Labile Toxin B Subunit That Separates Toxoid-Mediated Signaling and Immunomodulatory Action from Trafficking and Delivery Functions

  2003cites this paper
• Modulation of dendritic cell endocytosis and antigen processing pathways by Escherichia coli heat-labile enterotoxin and mutant derivatives.

  2003cites this paper
• The Cholera Toxin B Subunit Directly Costimulates Antigen‐Primed CD4+ T Cells Ex Vivo

  2003cites this paper
• Contribution of the ADP-ribosylating and receptor-binding properties of cholera-like enterotoxins in modulating cytokine secretion by human intestinal epithelial cells.

  2002cites this paper
• Antigen binding to GM1 ganglioside results in delayed presentation: minimal effects of GM1 on presentation of antigens internalized via other pathways

  2002cites this paper
• Evidence for a role of ganglioside GM1 in antigen presentation: binding enhances presentation of Escherichia coli enterotoxin B subunit (EtxB) to CD4(+) T cells.

  2001cites this paper
• Parasite-Host Interaction: A New Point of View on Immune Regulation

  2001cites this paper
• Cholera toxin and Escherichia coli enterotoxin B‐subunits inhibit macrophage‐mediated antigen processing and presentation: evidence for antigen persistence in non‐acidic recycling endosomal compartments

  2001influential citation
• Escherichia coli Heat-Labile Enterotoxin B Subunit Is a More Potent Mucosal Adjuvant than Its Closely Related Homologue, the B Subunit of Cholera Toxin

  2001cites this paper
• Genetically Manipulated Bacterial Toxin as a New Generation Mucosal Adjuvant

  2001cites this paper
• PARASITE-HOST INTERACTION: A NEW POINT OF VIEW ON IM-

  2001cites this paper
• Immunomodulation Using Bacterial Enterotoxins

  2001cites this paper
• Bacterial modulation of antigen processing and presentation.

  2000cites this paper
• Cholera toxin and related enterotoxins: a cell biological and immunological perspective.

  2000cites this paper
• Adjuvant effects of cholera toxin b subunit on immune response to recombinant thyrotropin receptor in mice.

  2000cites this paper
• Mechanisms of vaccine adjuvanticity at mucosal surfaces

  2000influential citation
• Immune modulation by the cholera-like enterotoxin B-subunits: from adjuvant to immunotherapeutic.

  2000cites this paper
• Oral administration of cholera toxin B-insulin conjugates protects NOD mice from autoimmune diabetes by inducing CD4+ regulatory T-cells.

  1999cites this paper
• MHC class I- and class II-restricted processing and presentation of microencapsulated antigens.

  1999cites this paper
• Cholera Toxin Suppresses Interleukin (IL)-12 Production and IL-12 Receptor β1 and β2 Chain Expression

  1999cites this paper
• Immune modulation by the cholera-like enterotoxins: from adjuvant to therapeutic.

  1999cites this paper
• Phagocytic antigen processing and effects of microbial products on antigen processing and T‐cell responses

  1999cites this paper
• Role of macrophage cytokines in mucosal adjuvanticity.

  1999cites this paper
• Sous-unite b de verotoxine destinee a une immunisation

  1999cites this paper
• Direct effects on antigen-presenting cells and T lymphocytes explain the adjuvanticity of a nontoxic cholera toxin mutant.

  1999cites this paper
• Current status of a mucosal vaccine against dental caries.

  1999cites this paper
• Cholera toxin increases intracellular pH in B lymphoma cells and decreases their antigen‐presenting ability

  1999cites this paper
• Importance of receptor binding in the immunogenicity, adjuvanticity and therapeutic properties of cholera toxin and Escherichia coli heat-labile enterotoxin

  1998cites this paper
• Effectiveness of Liposomes Possessing Surface-Linked Recombinant B Subunit of Cholera Toxin as an Oral Antigen Delivery System

  1998cites this paper
• Effect of route of immunisation and adjuvant on T and B cell epitope recognition within a streptococcal antigen.

  1998cites this paper
• Inhibition of Class II Major Histocompatibility Complex Antigen Processing by Escherichia coli Heat-Labile Enterotoxin Requires an Enzymatically Active A Subunit

  1998cites this paper
• Cholera toxin stimulates human B-cell DR antigen biosynthesis at the level of translation.

  1997cites this paper
• The mechanism of cholera toxin adjuvanticity.

  1997cites this paper
• Antigen processing differences among APC.

  1997cites this paper
• Mucosal immunogenicity of a recombinant Salmonella typhimurium-cloned heterologous antigen in the absence or presence of coexpressed cholera toxin A2 and B subunits

  1997cites this paper
• Genetically engineered nontoxic vaccine adjuvant that combines B cell targeting with immunomodulation by cholera toxin A1 subunit.

  1997cites this paper