Differential induction of help and suppression in mice by bifunctional antigens administered via different routes.

Bifunctional antigens composed of one L-tyrosine-p-azobenzenearsonate (Tyr-ABA) carrier epitope and one dinitrophenyl (DNP) haptenic epitope separated by 6-aminocaproyl or polyprolyl spacers induced weak IgM anti-DNP plaque-forming cell (PFC) responses in the spleens of mice immunized intraperitoneally, without detectable IgG PFC. However, the same antigens introduced into the footpads induced IgG PFC responses in the draining lymph nodes which rose to levels greater than 100/10(6) viable lymphocytes. Moreover, the response in the lymph nodes to booster injections of antigen was characteristic of secondary T-dependent antibody responses, whereas the splenic secondary response simply mirrored the primary. The magnitude of the IgG PFC response was influenced by the size of the spacer and by the strain of mice, although genetic control did not map to the major histocompatibility complex. Prior i.p. immunization suppressed the IgG response to subsequent immunization in the footpads. This suppression could be transferred to normal syngeneic recipient mice with spleen cells from suppressed donors. Suppressor activity was eliminated by treating the spleen cells with anti-Thy-1 antibody prior to transfer, establishing the T-cell dependency of suppression. Suppression was also induced by Tyr-ABA itself, but not by DNP-lysine, indicating the epitope specificity of the suppressor cells. Thus, bifunctional antigens induce dominant suppression in the spleen but significant help in lymph nodes.