The synthetic random polymers poly(Glu,Lys,Phe), poly(Glu,Phe) and poly (Glu,Lys,Tyr), have been used to study some parameters associated with the genetic control of the immune response (Ir) of mice. Mice of haplotypes d and q respond well to GLPhe. Mice of haplotypes k and b were previously shown to be nonresponders, whereas the F1 (k X b) responded via a phenomenon involving "complementation" between 2 Ir genes, i.e., one gene product from IA, and another from IE form the requisite two-chain Ia "receptor" macromolecules (E$ Et).
When it was determined that mice of haplotypes q and k respond to GPhe, and the controlling gene maps to IA, (A, Ao), we tested the theory that mice having q and k alleles in IA might respond to GLPhe via recognition of GPhe determinants in the terpolymer. Employing the in oitro proliferative response to T-cells from mice immunized with GLPhe and stimulated with GPhe and GLT (cross-reaction), it was determined that different determinant selection patterns exist in the recognition of GLPhe. Mice having q and k alleles in IA can respond to GLPhe via one mechanism, and other mice having d and f alleles respond via other mechanisms. The F1 of the appropriate nonresponder strains forming the Ia molecule (El Eft) still exhibit the "complementation" phenomenon. Rabbit antibody against anti-GPhe (ID) from SWR mice (H-Bq)(anti-ID) was prepared. This anti-ID strongly inhibited the binding of lZ5I-GPhe by anti-GPhe antisera produced only in mice of H-2q haplotype and had no effect on the binding of GPhe by anti-GPhe antisera produced in mice of other haplotypes. The anti-ID also inhibited the binding of lZ5I-GLPhe and lZ5I-GPhe by anti-GLPhe antisera produced only in mice of H-2s haplotype. These specificities were also confirmed by the inhibition of the plaque-forming cells. It was concluded that the antibodies produced in mice of H-2s haplotype against GPhe and GLPhe share common idiotypic determinants that are recognized by the anti-idiotypic antiserum.