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 (alpha Igh-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-alpha Id+) soluble factor (TsF1) released by effector-phase, Ts-2 suppressor cells. Each of these soluble suppressor factors requires homology in the Igh-V region to complete its regulatory functions. Our alpha Igh-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.
Hines
W H
WH
Department of Medicine, University of Pennsylvania, Philadelphia 19104.
Mann
R A
RA
Neilson
E G
EG
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D002846:Chromatography, Affinity; D000939:Epitopes / Q000276:immunology*; D006968:Hypersensitivity, Delayed; D007116:Immunization, Passive; D007143:Immunoglobulin Heavy Chains / Q000276:immunology*; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000276:immunology*; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D009395:Nephritis, Interstitial / Q000276:immunology*; D013491:Suppressor Factors, Immunologic / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D000939:Epitopes; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D013491:Suppressor Factors, Immunologic