Thymus-independence of Slowly Metabolized Immunogens

The role of thymus in antibody responses to a series of four synthetic polypeptide immunogens of the general formula multi-copoly(Tyr,Glu)-poly(Pro)-poly(Lys) was investigated as a function of the optical activity of the amino acids composing their structure. Irradiated nonthymectomized and thymectomized SJL mice were injected with thymocytes, marrow cells, or a mixture of both. Each group of recipients was immunized with the following copolymer enantiomorphs: all L-amino acids; L-amino acids outside and D inside; D-amino acids outside and L inside; or all D-amino acids. The antibody response to the immunogen composed of all L-amino acids was thymus-dependent, whereas the responses to the other three copolymers were all independent of the thymus. Similar cell transfers were performed in DBA/1 mice immunized with multi-copoly(L-Phe,L-Glu)-poly(D-Pro)-poly(D-Lys). This mouse strain produces specific antibodies against the (Phe,Glu) region and against the poly(D-prolyl) region. The immune response to the determinant with only L-amino acids on the outside was thymusdependent, whereas the response to the inside immunopotent region with only D-amino acids was thymusindependent. Since earlier studies have demonstrated that synthetic polypeptide antigens that contain D-amino acids are poorly metabolized, the thymus-independence of the antibody responses to these multichain synthetic polypeptides that possess repeating antigenic determinants was correlated with the metabolizability of the immunogens or their component determinants.