Serological analysis of idiotypic determinants on monoclonal antibodies specific to poly(Tyr,Glu)-poly(DLAla)--poly(Lys) and its ordered analogue (Tyr-Tyr-Glu-Glu)-poly(DLAla)--poly(Lys).

Anti-idiotypic sera (aIds) were raised in C57BL/6 mice against monoclonal antibodies (McAbs) which bind poly(Tyr,Glu)-poly(DLAla)--poly(Lys)--abbreviated to (T,G)-A--L--and (Tyr-Tyr-Glu-Glu)-poly(DLAla)--poly(Lys)--abbreviated to (T-T-G-G)-A--L--(nos. 103 and 160) and McAbs which react only with (T-T-G-G)-A--L (nos. 100 and 114). Anti-Id antibodies against 103 McAb reacted with (T,G)-A--L specific antibodies and specifically inhibited their binding to iodinated antigen. Similarly, conventional antibodies against the major idiotypes of (T,G)-A--L-specific antibodies inhibited the binding of 103 McAb to antigen. It is therefore suggested that 103 McAb shares major idiotypes with (T,G)-A--L-specific polyclonal antibodies of C3H.SW origin. Anti-Ids against 114 McAb also inhibited the binding of (T,G)-A--L-specific antibodies to antigen, but the binding of 114 McAb could not be inhibited by conventional aIds. Therefore, idiotypes of 103 and 114 McAbs define idiotypic determinants expressed on two different subpopulations of (T,G)-A--L-specific antibodies: those that carry major idiotypes and those which express idiotypic determinants other than the major one (minor Ids). Anti-idiotypic sera against McAbs nos. 100 and 160 reacted with the homologous idiotypes and not with the major idiotypes of (T,G)-A--L-specific antibodies. In addition to the aforementioned specificities we could define cross-reactive idiotypes (private) shared by McAbs nos. 100, 103 and 114 McAbs nos. 160 and 114. The analysis of idiotypes expressed on anti-(T,G)-A--L McAbs enabled the detection of new antigen binding site related idiotypic determinants in addition to the major idiotypes which were immunodominant in the polyclonal anti-(T,G)-A--L antibodies.