Specificity of genes controlling immune responsiveness to (T,G)-A-L and (Phe,G)-A-L.

Mice possessing the H-2b haplotype are high responders to the cross-reactive antigens (T,G)-A--L and (Phe,G)-A--L whereas mice with the H-2k haplotype respond only to (Phe,G)-A--L. On the level of cross-immunization we have demonstrated that either (Phe,G)-A--L or (T,G)-A--L primed high responder C3H.SW (H-2b) mice could be boosted with both antigens. On the other hand, low responder C3H/DiSn (H-2k) mice which were primed to (Phe,G)-A--L and thus possess (T,G)-A--L specific antibodies, could not be boosted with (T,G)-A--L to mount a secondary response. Only (Phe,G)-A--L primed and boosted H-2k mice produced high levels of (T,G)-A--L reactive antibodies. Furthermore, the binding of the anti-(Phe,G)-A--L antibodies of either C3H/DiSn or C3H.SW mice to 125I-(T,G)-A--L was better inhibited by guinea-pig anti-idiotypes than the binding of C3H.SW anti-(T,G)-A--L antibodies which are the homologous idiotypes (T,G)-A--L was found to be an equally efficient tolerogen in both high and low responder mice. Thus, when C3H.SW and C3H/DiSn mice were injected with a tolerogenic dose of (T,G)-A--L and then immunized with (Phe,G)-A--L, they were found to be tolerant to (T,G)-A--L antigenic determinants, since they produced only the unique antibodies to (Phe,G)-A--L. These results suggest that the H-2 linked Ir genes controlling antibody response to (T,G)-A--L are not involved in the induction of tolerance to (T,G)-A--L.