PCA Reactions in Guinea Pigs: Elicitation by Antigens of Related Structure and Inhibition by Haptens

Peptide determinants with the structure D-Alan-Gly (n = 1 or 3) conjugated to ribonuclease were used to elicit in rabbits specific anti-peptide antibodies which precipitated with rabbit serum albumin (RSA) conjugates, containing the same peptides. These antibodies injected into the skin of guinea pigs produced typical passive cutaneous anaphylaxis (PCA) reactions when the guinea pigs were challenged with the RSA conjugates. Cross-reactivity between the alanyl determinants was evaluated by challenging guinea pigs with RSA conjugates containing alanyl moieties which were either identical (homologous) or different (heterologous) from the alanine peptide in the immunogen. Elicitation of PCA with a dose of 2 mg of either the homologous or the heterologous antigens resulted in PCA reactions of equal size in the majority of cases. However, when 20 µg of the same RSA conjugates were employed, threshold amounts of antibodies were definitely lower when homologous antigen than when heterologous antigens were used. When series of free alanine peptides were injected intravenously to sensitized guinea pigs, it was found that in each system the homologous peptide was the most efficient inhibitor. In general, the degree of cross-reactions and susceptibility to inhibition by peptides were similar in precipitin tests and in PCA reactions. The results indicate that in addition to the immunodominant region other portions of the antigenic determinant contribute in a measurable degree to the activation of the antibody molecule for inducing histamine release.