Idiotypic determinants on human T cells and modulation of human T cell responses by anti-idiotypic antibodies.
The role of idiotypic anti-idiotypic interactions in the regulation of the human T cell response to tetanus toxoid (TT) antigen was examined in three subjects. Rabbit anti-idiotypic (anti-Id) antisera were raised against IgG (Fab')2 anti-TT obtained 7 to 10 days after booster immunization with TT. F(ab')2 fragments of rabbit-anti-Id IgG were used in conjunction with fluorescein-conjugated goat anti-rabbit Ig in an indirect immunofluorescence assay to determine the frequency of Id-positive cells in T cell-enriched preparations. This frequency was 24, 29, and 38 per 10,000, respectively, in the three subjects studied. Significant contribution of contaminating B cell to fluorescence-staining was ruled out by capping experiments using goat anti-human Ig (GAHIG) and by double staining experiments using rhodamine-conjugated GAHIG. Absorption of anti-Id antisera with Epstein Barr virus (EBV)-transformed B cell lines from the IgG (Fab')2 anti-TT donor, but not with EBV-B cell lines from unrelated donors, removed their reactivity with the T cells. Rabbit anti-Id IgG caused minimal proliferation (two-threefold) of T cells and had no effect on T cell proliferation in response to TT antigen when added to the cultures. Preincubation of T cells for 48 hr with rabbit anti-Id IgG (Fab')2, but not with preimmune rabbit IgG (Fab')2, resulted in the generation of antigen-specific suppressor cells that inhibited T cell proliferation in response to TT, but not in response to diphtheria toxoid (DT). These cells also inhibited the synthesis of IgG anti-TT in response to in vitro stimulation with TT antigen, but not the synthesis of IgG anti-DT in response to DT antigen. Adsorption of T cells over plates coated with rabbit anti-Id IgG (Fab')2 enhanced the proliferative response of the T cells to TT, but not to DT antigen, and enhanced the helper activity of the T cells for the in vitro synthesis of IgG anti-TT but not of IgG anti-DT antibodies. These results suggest that idiotypic-anti-idiotypic interactions play a role in the human T cell response to antigen.
D000042:Absorption; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D001402:B-Lymphocytes / Q000378:metabolism; D001666:Binding Sites, Antibody; D000939:Epitopes; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D008213:Lymphocyte Activation; D011817:Rabbits; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013745:Tetanus Toxoid / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000942:Antigens, Bacterial; D000939:Epitopes; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D013745:Tetanus Toxoid