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 lgG 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 pharmaco‐logical applications. © 1993 Wiley‐Liss, Inc.