Hapten-coupled monoclonal anti-I-A antibodies provide a first signal for the induction of suppression.

A mechanism for induction of hapten-specific immune unresponsiveness is described that utilizes a hapten-conjugated monoclonal anti-Ia antibody to direct the in vivo immune response. Azobenzenearsonate- (ABA) coupled anti-I-Ak antibodies provide a potent first signal for the induction of nonresponsiveness to ABA in H-2k,a mice. The use of an anti-Ia antibody requires haplotype matching and may selectively direct the hapten signal, because other haptenated monoclonal antibodies are ineffective. There is an absolute requirement for a second signal to achieve in vivo suppression; the signal may be substituted by the generation of an allogeneic effect at the time of hapten presentation. We suggest that these methods allow for specific targeting of hapten-suppressive signals that differ considerably from other model systems of tolerance to haptenated immunoglobulins. The results are discussed in relation to a potential role for an Ia+ cell involved in the induction of regulating suppressor pathways.