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 res ponses to recombinant preparations of B-subunits of Escherichia coli h eat-labile enterotoxin (rEtxB) and cholera toxin (rCtxB) is reported. Oral delivery of rEtxB to congenic mice of several different H-2 haplo types 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 re sponses in those strains tested Responses to rEtxB and rCtxB were foun d to be differentially modulated by the H-2 locus, with significant di fferential 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 mic e produced an H-2 dependent spectrum of responses characteristic of th ose elicited by rEtxB, with the antibodies predominantly directed agai nst 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, i mmunoregulation of antibody responses to rEtxB by intra-H-2 I-E in mic e transgenic for the entire IE(a)(k) gene was investigated. No signifi cant 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 resul ts for the design of vaccines against enterotoxigenic E. coli and chol era diarrhoea are discussed.