STUDIES ON ANTIGENICITY. THE RELATIONSHIP BETWEEN IN VIVO AND IN VITRO ENZYMATIC DEGRADABILITY OF HAPTEN-POLYLYSINE CONJUGATES AND THEIR ANTIGENICITIES IN GUINEA PIGS.

The enzymatic degradation of fluorescein conjugates of poly-L-lysine, poly-D-lysine, and exhaustively succinylated poly-L-lysine by aqueous extracts of spleens from "responder" (guinea pigs which can develop immune responses to hapten-poly-L-lysine conjugates) and "non-responder" guinea pigs was investigated. The in vivo degradation of H(3)-tagged dinitrophenyl conjugates of these synthetic polyamino acids was also studied by measuring urinary excretion of radioactive low molecular weight degradation products of these conjugates after their intraperitoneal injection. It was found that both responder and non-responder guinea pigs can degrade succinylated and unsuccinylated poly-L-lysine conjugates into small molecular fragments, but they cannot degrade hapten-poly-D-lysine conjugates. These studies demonstrate that in addition to the known requirements for antigenicity of macromolecules, i.e. the presence of antigenic determinants, and their capacity to be degraded by immunological tissues, the resulting degradation products must undergo certain additional, as yet unidentified, specific metabolic steps in order to induce an immune response.