Studies on the mechanism of antigenic competition: Analysis of competition between synthetic polypeptide antigens

Antigenic competition has been studied in C3H/HeJ mice between determinants of the multichain synthetic polypeptide antigens, (Phe, G)‐A–L, (T, G)‐Pro–L and (Phe, G)‐Pro–L. Since these mice did not respond detectably to (T, G) and only very weakly to A–L, the relevant immunopotent regions involved were Pro – L and (Phe, G). Thus, these animals generated a good response to the (Phe, G) determinant, when given as (Phe, G)‐A–L, and a good response to Pro – L, when administered either as such or as (T, G)‐Pro–L. However, when the immunogen was (Phe, G)‐Pro–L, the antibody response was mainly towards Pro–L, whereas a very poor response was obtained to the (Phe, G) specificity. This is interpreted as antigenic competition between Pro–L and (Phe, G), with Pro–L the dominant and (Phe, G) the suppressed determinant. Competition was also demonstrated with mixtures of (T, G)‐Pro–L and (Phe, G)‐A–L. Competition with the mixed antigens was dependent on the relative amounts of the immunogens in the mixtures. Thus, a molar excess of (T, G)‐Pro–L over (Phe, G)‐A–L of 5 to 1 suppressed the response to (Phe, G), but an excess of (Phe, G)‐A–L of 5 to 1 suppressed the of 25 to 1 caused suppression of the anti‐Pro–L response. With equimolar mixtures, an optimal primary response to both (Phe, C) and Pro–L was observed. Where competition had occurred in the primary response, no priming was detected for a secondary response. Under certain conditions immunological memory could be suppressed by competition even though an apparently normal primary response had occurred, suggesting that memory is more susceptible to suppression by competition than is the primary response. The ability of an excess of (Phe, G)‐A–L to suppress the response to Pro–L could be reproduced completely with A–L alone. Thus, a molecule that is very poorly immunogenic, but which functions as a carrier for haptens, can be successful in competition.