Studies on the relation of a prior immune response to immunogenicity.

(1) Two polymers of D-glutamic acid, one synthetic (poly-α-D-glutamic) and the other the capsular polypeptide of (poly-γ-D-glutamic), which did not induce detectable antibody when injected in saline, elicited precipitating antibody in rabbits when complexed with methylated bovine serum albumin (MBSA). (2) Animals that had made an immune response to either of the polypeptides did not produce detectable anti-hapten antibodies when subsequently immunized with the homologus polypeptide conjugated with -amino--dimethylaminoazobenzene (PDA) groups. Neither was there an observable response to the polypeptide carrier. (3) Hapten-specific antibody was elicited with an immunogenic carrier, hen egg albumin, and with the polypeptide—PDA conjugates complexed with MBSA, demonstrating that PDA could act as a determinant under the appropriate conditions. (4) Rabbits that had made PDA-specific antibody were entirely refractory to polypeptide—PDA conjugate, inasmuch as their levels of anti-PDA antibody remained unchanged. (5) It is concluded that the formation of antibody against a weakly immunogenic molecule does not alter the state of responsiveness of the animal upon subsequent contact with that molecule. Such a molecule cannot serve as a carrier for another structural determinant, either in animals that have made a prior immune response to the carrier or to the determinant.