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 Esc herichia coli heat-labile enterotoxin B subunit (EtxB) was tested by c omparing its immunogical properties with those of a receptor binding m utant, EtxB(G33D). Subcutaneous immunization of EtxB(G33D) resulted in 160-fold reduction in antibody titer compared with wild-type EtxB, wh ereas its oral delivery failed to provoke any detectable secretory or serum anti-B subunit responses. Moreover, the two proteins induced str ikingly different effects on lymphocyte cultures in vitro. EtxB, in co mparison with EtxB(G33D), caused an increase in the proportion of B ce lls, 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, sugg esting that its potent immunogenicity is dependent not only on efficie nt receptor-mediated uptake, but also on direct receptor-mediated immu nomodulation of lymphocyte subsets.