Role of epitope density in the induction of immunity and tolerance with thymus-independent antigens. II. Studies with 2,4-dinitrophenyl conjugates in vivo.

The immunogenicity and tolerogenicity of 2,4-dinitrophenyl (DNP) conjugates of levan, type 3 pneumococcal polysaccharide (SIII), dextran B512 and dextran B 1299 with different levels of substitution were assessed in vivo. It was confirmed that, as in vitro, conjugates with low epitope density are solely immunogenic for Bmu cells, whereas higher density conjugates are both immunogenic and tolerogenic according to dosage. The maximal anti-DNP plaque-forming cell responses attainable varied by 2 log10 according to the carrier, being greatest with dextrans and least with SIII. The effect of the carrier on immunogenicity was not attributable to B cells responding to it, as concurrent tolerization by either free polysaccharide or the conjugate itself was without effect. Optimal immunization was succeeded by varying degrees of responsiveness ("exhaustion") which was greatest with the more immunogenic conjugates. In contrast, reduction of tolerizing dose by cyclophosphamide suppression was only a feature of more highly substituted conjugates.