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

The effect of different degrees of conjugation of levan, dextran, pneumococcal polysaccharide SIII and the copolymer of D-glutamic acid and D-lysine with the 2,4-dinitrophenyl determinant (DNP) on the immunogenic and tolerogenic capacity of its haptenic conjugates was investigated in vitro. A strikingly uniform effect of hapten conjugation was observed despite the marked difference in the mol. wt. and structure (branched or linear) of the carrier molecules. Regarding the anti-DNP response, low density conjugates were immunogenic but not tolerogenic (even at high doses), higher conjugates were both, depending on concentration, while very high density conjugates were only tolerogenic. These results confirm and extend earlier findings made with DNP conjugates of polymeric flagellin and indicate the probable generality of this principle. Together with parallel in vivo studies (Eur. J. Immunol. 1975. 5:541), they reaffirm the importance of epitope density in the discrimination between immunity and tolerance.