AbstractThe immune response of two inbred mouse strains, DBA/1 and SJL, to eight synthetic polypeptides of the general formulae, poly(Tyr, Glu)‐poly Pro—polyLys and poly(Phe, Glu)‐polyPro—polyLys, differing in the optical configuration of the amino acids composing the macromolecules, was compared. SJL mice responded predominantly to the polyPro—polyLys moieties of either optical configuration in the eight enantiomorphs. In both strains of mice tested, immunization with polypeptides of the formula poly(Tyr, Glu)‐polyPro—polyLys leads to antibodies specific for the polyproline moiety mainly. DBA/1 mice are low responders to 701, poly(LTyr,LGlu)‐polyLPro—polyLLys, whereas they elicit a good immune response to polyDPro—polyDLys when immunized with 713, poly(DTyr, DGlu)‐polyDPro—polyDLys, and with 711, poly(LTyr,LGlu)‐polyDPro—polyDLys. It is of interest that mice of the DBA/1 strain responded well to 715, poly(DTyr, DGlu)‐polyLPro—polyLLys with antibodies specific to poly‐L‐proline. Since this polymer is metabolized slowly and incompletely similarly to antigens composed exclusively ofD‐amino acids, it is likely that the slow metabolism affects the ability of this mouse strain to respond to this immunogen.DBA/1 mice responded predominantly to the (LPhe,LGlu) region when immunized with 702, poly(LPhe,LGlu)‐polyLPro—polyLLys. Since they are high responders to (LPhe,LGlu) and to polyDPro—polyDLys, they elicited antibodies to both immunopotent regions of 712, poly(LPhe,LGlu)‐polyDPro—polyDLys. Although DBA/1 mice are high responders to (LPhe,LGlu) they did not respond toD‐amino acid analogues of these peptides, and immunization of this mouse strain with 714, poly(DPhe,DGlu)‐polyDPro—polyDLys, and with 716, poly(DPhe,DGlu)‐polyLPro—polyLLys, elicited anti‐polyproline antibodies only.The results of this study show that the optical configuration of the amino acids composing an antigen plays an important role in the genetic contr