Immunoregulatory role of H-2 and intra-H-2 alleles on antibody responses to recombinant preparations of B-subunits of Escherichia coli heat-labile enterotoxin (rEtxB) and cholera toxin (rCtxB)

The immunoregulatory role of H-2 and intra-H-2 alleles on antibody responses to recombinant preparations of B-subunits of Escherichia coli heat-labile enterotoxin (rEtxB) and cholera toxin (rCtxB) is reported. Oral delivery of rEtxB to congenic mice of several different H-2 haplotypes resulted in H-2 dependent serum IgG responses (H-2(d) > H-2(b) = H-2(q) > H-2(a) > H-2(k)) and a similar spectrum of intestinal IgA responses in those strains tested Responses to rEtxB and rCtxB were found to be differentially modulated by the H-2 locus, with significant differential effects in H-2(b) and H-2(d) congenic strains (H-2(d) > H-2(b) for rEtxB; H-2(b) > H-2(d) for rCtxB), Additionally, it was found that when rEtxB was fed to mice previously primed (orally) with either rEtxB or rCtxB only those mice primed with rEtxB exhibited a booster response. A second booster immunisation with rEtxB in rCtxB-primed mice produced an H-2 dependent spectrum of responses characteristic of those elicited by rEtxB, with the antibodies predominantly directed against rEtxB and not rCtxB. These results indicate that the differential response to rEtxB and rCtxB is set at the T- and B-cell level. Also, immunoregulation of antibody responses to rEtxB by intra-H-2 I-E in mice transgenic for the entire IE(a)(k) gene was investigated. No significant difference between responses in transgene-positive and -negative mice was found, suggesting that antigen presentation does not involve I-E, but occurs in the context of I-A. The implications of these results for the design of vaccines against enterotoxigenic E. coli and cholera diarrhoea are discussed.