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Potent immunogenicity of the B subunits of Escherichia coli heat-labile enterotoxin: Receptor binding is essential and induces differential modulation of lymphocyte subsets
journal contribution
posted on 2023-06-10, 04:07 authored by T O Nashar, Helen WebbHelen Webb, S Eaglestone, N A Williams, T R HirstThe 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 ?. 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.
History
Publication status
- Published
Journal
Proceedings of the National Academy of Sciences (PNAS)ISSN
0027-8424Publisher
National Academy of SciencesExternal DOI
Issue
1Volume
93Page range
226-230Event location
United StatesDepartment affiliated with
- Biochemistry Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2022-07-01Usage metrics
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No categories selectedKeywords
AdjuvantsImmunologic;Animals;AntibodiesBacterial;Bacterial Toxins;Base Sequence;Cytokines;DNA Primers;Enterotoxins;Escherichia coli;Escherichia coli Proteins;G(M1) Ganglioside;Immunologic Capping;Immunophenotyping;Lymphocyte Activation;Lymphocyte Subsets;Mice;MiceInbred BALB C;Molecular Sequence Data;MutagenesisSite-Directed;ReceptorsCell Surface;Structure-Activity Relationship
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