Novel mechanisms of specific suppression of anti-hapten antibody response mediated by monoclonal anti-carrier antibody.
The cellular mechanisms of the antibody-induced suppression of immune responses were analyzed in the keyhole limpet hemocyanin (KLH) system. Some of the monoclonal anti-KLH antibodies, like KLH-specific suppressor T cell factor (KLH-TsF), were demonstrated to suppress the anti-2,4-dinitrophenyl IgG but not IgM plaque-forming cell responses in a KLH-specific and H-2-restricted manner. The anti-KLH antibodies with suppressive activity reacted with, and in turn, stimulated the suppressor hybridoma (34S-281) with the anti-idiotypic receptor complementary to the idiotypic KLH-TsF of the inducer type. Moreover, because the suppressive activity of the anti-KLH antibody was completely abolished by the treatment of responding spleen cells with anti-Lyt-2 and complement, it was apparent that the suppressive antibody activated suppressor T cell pathways. The isotype or affinity of antibodies is not related to the suppressive activity, because suppressive and nonsuppressive antibodies possess a similar affinity belonging to the same Ig isotypes. It also has been demonstrated that the Fc portion is not the functional site, because the F(ab')2 fragment still has the activity. The antibody specificity is found to be important for determining whether the antibody is suppressive or not. In fact, anti-KLH 26, but not other antibodies without activity, recognizes the particular KLH epitope seen by KLH-TsF, and exclusively interacts with the anti-idiotypic suppressor T cells. Thus, the anti-idiotypic suppressor T cell receives signals both from the suppressive anti-KLH antibody and from KLH-TsF, and transmits the antibody-induced suppressor signals to the effector-suppressor pathway. The size of the repertoire of anti-idiotypic suppressor T cells involved in the suppression seems to be very limited, because only four out of 120 monoclonal anti-KLH antibodies were found to have suppressor activity. The possible mechanisms of the cell interaction mediated by the suppressive antibody are discussed.
Sumida
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Taniguchi
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000502:physiology*; D006241:Haptens / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D007108:Immune Tolerance; D007117:Immunization, Secondary; D007140:Immunoglobulin Fab Fragments / Q000502:physiology; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007130:Immunoglobulin Idiotypes / Q000276:immunology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000276:immunology; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D013491:Suppressor Factors, Immunologic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D000911:Antibodies, Monoclonal; D006241:Haptens; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D008222:Lymphokines; D013491:Suppressor Factors, Immunologic; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin