Antigenic competition and genetic control of the immune response. A hypothesis for intramolecular competition

A study has been made of antigenic competition between the (Phe,Glu) and Pro-Lys regions of three synthetic multichain polypeptides, (Phe,Glu)-Ala-Lys, (Tyr,Glu)-Pro-Lys and (Phe,Glu)-Pro-Lys. Two strains of mice have been compared, C3H/HeJ, potentially high responders to both (Phe,Glu) and Pro-Lys, and DBA/1, high responders to (Phe,Glu), but genetic low responders to Pro-Lys. In C3H/HeJ, both intramolecular competition, within the (Phe,Glu)-Pro-Lys molecule, and intermolecular competition, with mixtures of (Tyr,Glu)-Pro-Lys and (Phe,Glu)-Ala-Lys occur. In general, Pro-Lys is the dominant determinant and suppresses the response to (Phe, Glu). In DBA/1, on the other hand, intramolecular competition is absent, but intermolecular competition is still present. The injection of the polyribonucleotide poly (A)·poly (U) corrects the low response to Pro-Lys in DBA/1, and at the same time restores intramolecular competition. Intramolecular competition is, therefore, related to the level of the antibody response to the dominant antigenic region, Pro-Lys. In contrast, intermolecular competition is independent of the antibody response to Pro-Lys, but is related to the ratio of the antigens (Tyr,Glu)-Pro-Lys and (Phe,Glu)-Ala-Lys in the mixture injected.A model is suggested in which intramolecular competition is a result of competition between specific B cells for limiting antigen. The model relates competition to original antigenic sin and the enhancement and suppression mediated by antibody. Intermolecular competition seems to have a different mechanism and to be a T cell effect. The relevance of these findings to studies on the genetic control of the immune response is discussed.