Antigenic competition between polypeptidyl determinants in normal and tolerant rabbits.

Competition between two polypeptidyl determinants was studied in normal rabbits and rabbits made tolerant to the competing antigen. The capacity of poly-DL-phenylalanyl protein conjugate to inhibit the formation of antibodies specific to the poly-DL-alanyl determinant was dependent on the nature of the protein carrier of the singly substituted antigens. Competition occurred only when the peptidyl determinants were attached to identical or similar (RSA and HSA) carriers. Thus, the immune response toward the poly-DL-alanyl determinant was impaired by injecting the pairs p-DL-PheRSA and p-DL-AlaHSA, or p-DL-PheRNase and p-DL-AlaRNase. Suppression of the formation of antibodies with poly-DL-alanyl specificity was not observed, however, upon administration of p-DL-PheRSA together with p-DL-AlaRNase or of p-DL-PheRNase with p-DL-AlaHSA. Tolerance to p-DL-PheRSA was induced by injecting this material into newborn rabbits. The tolerant animals retained their capacity to produce anti-poly-DL-alanyl antibodies upon injection of p-DL-AlaRSA or p-DL-AlaHSA. However, when these poly-DL-alanyl proteins were administered together with p-DL-PheRSA, antibodies against the poly-DL-alanyl determinant were not formed even though no antibodies with poly-DL-phenylalanyl specificity were produced. These results indicate that in competition experiments the preference in the immune response against a given determinant is dependent not only on the nature of the competing determinants, but it is also governed to a large extent by the over-all properties of the antigenic molecules. This suggests that at the stage at which the competition occurs the competing molecules had not undergone considerable degradation. On the basis of experiments with tolerant animals, it is suggested that in normal animals antibody formation to the competing antigen is not the cause of its inhibitory action on the response against the other antigen. The competition experiments described suggest that an antibody-forming cell is multipotent.