Murine interstitial nephritis. VIII. Characterization of Igh-V restriction determinants in the development of anti-idiotypic immunity using blocking antibodies

We have prepared antisera specific for Igh-V-linked determinants (αIgh-V) in order to study Igh-V restriction during the development of protective, T cell-mediated anti-idiotypic immunity in autoimmune interstitial nephritis. Suppressor T cells in this network use an antigen-binding (RE-Id⁺) factor (TsF₁) secreted by first-order suppressor cells (Ts-1) to induce an anti-idiotypic (RE-αId⁺) soluble factor (TsF₂) released by effectorphase, Ts-2 suppressor cells. Each of these soluble suppressor factors requires homology in the Igh-V region to complete its regulatory functions. Our αIgh-V antisera, adsorbed against network idiotypes, can interfere with the Igh-V restriction used in the induction of Ts-2 suppression by TsF₁. The antisera bind both TsF₁ and TsF₂ in an allele-specific manner and are cytotoxic to induced Ts-2 cells, but not their precursors. These Igh-V determinants appear to behave like activation molecules. They lie outside of the ligand-binding site, do not map with the serologic binding of idiotype, and thus act as distinct associative-recognition elements in the maturation of anti-idiotypic immunity.