Synthetic antigens composed exclusively of L- or D-amino acids. I. Effect of optical configuration on the immunogenicity of synthetic polypeptides in mice.

Two random linear co-polymers composed exclusively of D-amino acids were found to elicit a primary response in mice; the sera were assayed by the indirect precipitin reaction. 247, (D-Tyr, D-Glu, D-Ala) was studied intensively and compared to a similar polypeptide, 253, (L-Tyr, L-Glu, L-Ala), of opposite optical configuration. The primary response to the D-isomer in adjuvant is highly dose-dependent, showing a sharp maximum around 1 μg/mouse, while that to the L-isomer in adjuvant is largely dose-independent. At low doses the D-isomer is as immunogenic as the L-isomer. Re-injection of the D-isomer led to no increase in titre; re-injection of the L-isomer gave a typical secondary response. The antibodies formed to both isomers were highly stereospecific. The D-isomer was 50–1000 times as efficient at inducing paralysis as the L-isomer, and the paralysis was specific. The differences between the D- and L-isomers are thought to be explained by the much greater capacity of the D-isomer in inducing immunological paralysis.