Synthetic antigens composed exclusively of L- or D- amino acids. II. Effect of optical configuration on the metabolism and fate of synthetic polypeptide antigens in mice

Abstract

The immunogenic D-amino acid synthetic polypeptide, 247, p(D-Tyr, D-Glu, D-Ala), was shown to induce specific immunological paralysis in small doses in mice. The corresponding L-amino acid polypeptide, 253, p(L-Tyr, L-Glu, L-Ala) primes mice in similar doses. The metabolism and fate of these polymers were studied and correlated with their immunological activity in mice. Using ¹²⁵I as label, it was found that the D-polymer is broken down twenty-two times more slowly than the L-polymer; in addition some of the D-polymer appeared to be excreted intact in the urine. After footpad injection, 200–1000 times as much D-polymer as L-polymer was retained in draining lymph nodes and spleen. Much of the D-polymer is retained in the kidney, liver and injection site; the D-polymer in the kidney is localized in proximal convoluted tubule cells. Autoradiographs of sections of draining lymph nodes show the D-polymer localized almost exclusively in macrophages, while the L-polymer was found initially in macrophages and increasingly also in germinal centres, its presence in the latter being correlated with the appearance of circulating antibody.