A peptide sequence mimics the epitope on the multideterminant antigen (Tyr,Glu)-Ala-Lys that induces the dominant...

The multideterminant Ag (Tyr,Glu)-Ala-Lys [(T,G)-A-L] elicits a heterogeneous secondary antibody response to different epitopes consisting of side-chain or backbone residues. However, the primary response is restricted and dominated by side-chain specific antibodies that also bind a random, linear copolymer of L-Glu and L-Tyr (GT+ antibodies), share TGB5 Id, and use the H10/V kappa 1 germ-line gene combination. We analyzed several defined sequence peptides to determine whether any might mimic the side-chain epitope(s) on (T,G)-A-L which induce the dominant Id+, H10/V kappa 1+ primary response. A carrier conjugate of the peptide TyrGluGluGluGluTyrTyrGluGluGluGluTyr (called TG4) was recognized by all the (T,G)-A-L-induced, GT+ hybridoma antibodies analyzed. In the splenic focus assay, the majority of primary and memory B cell clones induced by (T,G)-A-L produced antibodies that recognized the TG4 peptide. Mice immunized with TG4 conjugated to human gamma globulin (HGG) produced antibodies that bound (T,G)-A-L and were TGB5 Id+. Molecular analysis of Id+ primary hybridomas from TG4-HGG immunized mice showed that the antibodies used the H10 and V kappa 1 germ-line genes. Thus, the TG4 peptide can be bound by Id+, GT+ anti-(T,G)-A-L antibodies, and it induces Id+ antibodies that use the H10/V kappa 1 gene combination. By these criteria, the TG4 peptide mimics the side-chain epitope(s) on (T,G)-A-L that induces the dominant primary antibody response to that multideterminant Ag.