A comparison of the immunogenicity of a pair of enantiomeric proteins.

The immunogenicity of a folded, all D-amino acid protein, rubredoxin, has been compared with that for the corresponding L-protein enantiomer. Following multiple administrations with alum adjuvant, the L-protein induced a strong, specific IgG antibody response, whereas the D-protein did not. This relative lack of responsiveness to the D-protein cannot be attributed to rapid excretion, since it is retained at least 4 times longer than the natural L-protein. These observations provide the first direct evidence that a folded D-amino acid protein has low immunogenicity and is long lived in vivo. Proteins with such properties may be useful as molecular platforms in a variety of chemical and pharmacological applications.