Potent immunogenicity of the B subunits of Escherichia coli heat-labile enterotoxin: Receptor binding is essential and induces differential modulation of lymphocyte subsets

Nashar, T O, Webb, H M, Eaglestone, S, Williams, N A and Hirst, T R (1996) Potent immunogenicity of the B subunits of Escherichia coli heat-labile enterotoxin: Receptor binding is essential and induces differential modulation of lymphocyte subsets. Proceedings of the National Academy of Sciences (PNAS), 93 (1). pp. 226-230. ISSN 0027-8424

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Abstract

The importance of receptor binding in the potent immunogenicity of Escherichia coli heat-labile enterotoxin B subunit (EtxB) was tested by comparing its immunogical properties with those of a receptor binding mutant, EtxB(G33D). Subcutaneous immunization of EtxB(G33D) resulted in 160-fold reduction in antibody titer compared with wild-type EtxB, whereas its oral delivery failed to provoke any detectable secretory or serum anti-B subunit responses. Moreover, the two proteins induced strikingly different effects on lymphocyte cultures in vitro. EtxB, in comparison with EtxB(G33D), caused an increase in the proportion of B cells, many of which were activated (CD25+); the complete depletion of CD8+ T cells; an increase in the activation of CD4+ T cells; and an increase in interleukin 2 and a decrease in interferon γ. These data indicate that EtxB exerts profound effects on immune cells, suggesting that its potent immunogenicity is dependent not only on efficient receptor-mediated uptake, but also on direct receptor-mediated immunomodulation of lymphocyte subsets.

Item Type: Article
Keywords: Adjuvants, Immunologic;Animals;Antibodies, Bacterial;Bacterial Toxins;Base Sequence;Cytokines;DNA Primers;Enterotoxins;Escherichia coli;Escherichia coli Proteins;G(M1) Ganglioside;Immunologic Capping;Immunophenotyping;Lymphocyte Activation;Lymphocyte Subsets;Mice;Mice, Inbred BALB C;Molecular Sequence Data;Mutagenesis, Site-Directed;Receptors, Cell Surface;Structure-Activity Relationship
Schools and Departments: School of Life Sciences > Biochemistry
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 01 Jul 2022 08:13
Last Modified: 01 Jul 2022 08:13
URI: http://sro.sussex.ac.uk/id/eprint/106694
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