A Ts cell subset has been identified in the spleens of responder mice 3 to 6 wk after immunization with an optimally immunogenic dose of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). These Ts were positively selected by panning procedures by using a mAb (1248 A4.10) produced by immunization of rats with semipurified mouse GAT-specific, single polypeptide chain suppressor factor. These Ts cells inhibited the activity of virgin Th cells but not memory Th cells and this activity was genetically restricted by genes which are linked to the Ig H chain (Igh) locus on chromosome 12. Use of the Igh recombination strain, BAB.14, which has a crossover near the V(H)C(H) region junction, demonstrated that the genes regulating the Igh restriction map telomeric to the V(H) genes. The Igh-linked restriction regulated the interaction of A4.10+ Ts cells with virgin T cells and not B cells. However, A4.10+ Ts did not act directly on Lyt-2- Th cells, but required the presence of Lyt-2+ cells for suppression. Suppression by GAT-primed A4.10+-Ts cells also required syngenicity at Igh-linked genes by both Lyt-2- and Lyt-2+ T cells. These results indicated that A4.10+-Ts cells were inducer Ts cells which activated Lyt-2+ effector Ts cells which prevented primary GAT specific Th cell activity. The interaction between A4.10+-Ts inducer and effector Ts cells and/or the interaction of the effector Ts and its target cell were restricted by genes linked to the Igh constant region.