Potent immunogenicity of the B subunits of Escherichia coli heat-labile enterotoxin: receptor binding is essential and induces differential modulation of lymphocyte subsets.
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 gamma. 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.
Nashar
T O
TO
Research School of Biosciences, University of Kent, Canterbury, Great Britain.
Webb
H M
HM
Eaglestone
S
S
Williams
N A
NA
Hirst
T R
TR
D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001427:Bacterial Toxins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers / Q000737:chemistry; D004768:Enterotoxins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology*; D029968:Escherichia coli Proteins; D005677:G(M1) Ganglioside / Q000502:physiology*; D007152:Immunologic Capping; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011956:Receptors, Cell Surface / Q000378:metabolism; D013329:Structure-Activity Relationship
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D016207:Cytokines; D017931:DNA Primers; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D011956:Receptors, Cell Surface; D005677:G(M1) Ganglioside; C027538:heat-labile enterotoxin, E coli