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

tIapten conjugates of synthetic poly amino adds are useful tools for the investigation of the metabolism of antigen, which is an early step in the immune response. Previous studies have shown that approximately 25 per cent of random-bred guinea pigs and 100 per cent of the highly inbred strain 2 guinea pigs are capable of developing an immune response to lightly coupled hapten-poly-L-lysine (PLL) conjugates (1-5). These animals have been termed "responders," whereas guinea pigs incapable of responding immunologically to hapten-PLL conjugates were termed "non-responders." The inability of non-responder guinea pigs to recognize hapten-PLL conjugates as antigen is not due to an absence of antigenic determinants in these conjugates, since these guinea pigs can synthesize antihapten antibodies when immunized with protein conjugates of these same haptenic determinants. Individual random-bred guinea pigs immunized with PLL 1 conjugates of 4 structurally unrelated haptens either show immune responses against all 4 haptens or against none (2). In addition, the ability to develop an immune response to haptenPLL conjugates was shown to be transmitted genetically as a unigenic, autosomal Mendelian dominant trait (3). These findings suggested that the difference between responder and non-responder guinea pigs may reside in their abilities to metabolize properly the PLL carrier. The genetic findings indicate further that the differences between responder and non-responder guinea pigs may be the presence, in responders, of a single essential metabolic enzyme, either an enzyme responsible for degradation of the PLL carrier (e.g. a cathepsin) or an enzyme involved in a subsequent metabolic operation on the PLL carrier, which leads to the formation of the specific inducer bearing the antigenic determinant.