Relation between optical configuration and immunogenicity of synthetic polypeptides

Abstract

Three random linear copolymers composed of two or three of the amino acids D-tyrosine, D-glutamic acid, D-alanine and D-lysine, and a branched multichain copolymer with a poly-D-lysine backbone and polymeric side chains of D-tyrosine and D-glutamic acid, were found to be non-antigenic in rabbits, by precipitin and passive cutaneous anaphylaxis, and in guinea pigs, by delayed hyper sensitivity tests. The corresponding four copolymers of L-amino acids were shown to be antigenic by all the three criteria. No immunological cross-reactions were observed between the polypeptides composed of D-amino acids and the corresponding L-amino acid copolymers. Similarly, an azobenzenearsonic acid conjugate of poly-D-tyrosine was shown to be non-antigenic in guinea pigs, in contrast with an analogous conjugate of poly-L-tyrosine. Animals sensitized with the conjugate of poly-L-tyrosine did not exhibit delayed skin reactions, when cross-tested with the D-conjugate. A linear polymer composed of D-tyrosine, L-glutamic acid and L-alanine was found to be immuno-genic and to cross-react with the corresponding polymer composed exclusively of D-amino acids.