The immune response to a synthetic polypeptide built on multichain polyproline, poly-L-(Tyr,Glu)-poly-L-Pro-poly-L-Lys [(T,G)-Pro--L], in the offspring of a cross between DBA/1 and SJL mice is under a genetic control superficially similar to the one operating for the immune response to a similar synthetic polypeptide built on multichain polyalanine, poly-L-(Tyr,Glu)-poly-D,L-Ala-poly-L-Lys [(T,G)-A--L], in the offspring of a cross between CBA and C57 mice. In both cases, the genetic control is a quantitative trait in which the major gene(s) is (are) dominant and the trait is not linked to any of the known structural genes coding for mouse immunoglobulin heavy chains. However, the genetic control of response to (T, G)-Pro--L, designated immune response-3 (Ir-3), is qualitatively different from the one operating for (T,G)-A--L [immune response-1 (Ir-1)] in that it is not linked to the histocompatibility-2 (H-2) locus. A study of the immune response to a related polypeptide built on multichain polyproline, poly-L-(Phe,Glu)-poly-L-Pro-poly-L--Lys [(Phe, G)-Pro--L], in the DBA/1 x SJL cross has shown a genetic control of antibody specificity. F1 x DBA/1 backcross anti-(Phe, G)-Pro--L sera segregate in their ability to bind (T,G)-Pro--L, and there is no linkage of anti-(T,G)-Pro--L binding capacity with the H-2s allele of the SJL grandparent. F1 x SJL anti-(Phe, G)-Pro-L sera segregate in their capacity to bind poly-L-(Phe,Glu)-poly-D,L-Ala-poly-L-Lys [(Phe, G)-A--L] and the ability to bind (Phe, G)-A--L is clearly linked to the H-2q allele from the DBA/1 grandparent. Thus, in mice all responding well to a given antigen [(Phe, G)-Pro--L], the specificity of the antibodies produced [i.e., anti-(Phe,G) or anti-prolyl] is genetically determined. Cross-inhibition of binding m (DBA/1 x SJL)F1 anti-(Phe,G)-Pro--L antisera indicates that the anti-(Phe,G) and anti-prolyl specificities are a function of two separate and largely non-crossreacting antibody populations.
The response of inbred mouse strains to two polypeptides derived from multichain polyprolines, (T,G)-Pro--L and (Phe,G)-Pro--L, is different from the response of the same mouse strains to a similar series of polymers built on multi-poly-D,L-alanyl--poly-L-lysine, although the same short sequences of amino acids are attached to the side chains of the polypeptides in the two series. These results indicate that a portion of the side chain (e.g. polyalanine or polyproline) participates in the antigenic determinant. This was confirmed by studying the response of different mouse strains to two kinds of polypeptides: (T,G)-Pro-A--L 717 and 718 and (T,G)-A-Pro--L 719 and 721. Antibody assay of antisera to (Phe,G)-Pro--L with the cross-reacting antigens (T,G)-Pro--L and (Phe,G)-A-L indicates that different inbred mouse strains make antibodies specific for different parts of the same polypeptide. Thus, antibody from DBA/1 mice reacts almost exclusively with the (Phe,G) sequence, while SJL antisera bind only (T,G)-Pro--L and fail to bind (Phe,G)-A-L. The immune responses to the same amino acids on two different polypeptides (i.e. A--L and Pro--L) appear to be under separate genetic control.