Characterization of two monoclonal idiotype-binding suppressor T cell factors specific for the antibody response to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT).

We have previously identified and described two distinct types of suppressor T cell factors specific for the PFC response to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) or L-glutamic acid50-L-tyrosine50 (GT). Both of these factors are antigen-specific and I-J+. GAT-TsF1 is not MHC-restricted and is composed of a single polypeptide chain, whereas GAT-TsF2 is MHC-restricted and is composed of two different polypeptide chains. We have not previously found evidence for an obligatory, idiotype-specific suppressor T cell in this suppressor pathway. However, we now report that idiotype-specific suppressor T cells can be elicited by exposing normal spleen cells to GAT-TsF1 or GAT-TsF2 in the absence of antigen in vitro. These factor (TsF1/TsF2)-induced cells have been fused with the AKR thymoma, BW5147, and hybridomas were selected for production of suppressor factors that inhibit GAT-specific antibody responses in vitro. In this report, we characterize one monoclonal factor from each fusion. Neither factor binds GAT or the related co-polymer, GT; both factors have binding sites for GAT-specific idiotypes but not for unrelated idiotypes either in the form of antibody immobilized on Sepharose or as cell surface determinants expressed by B cell hybridomas. Moreover, their reactivities for a panel of monoclonal anti-GAT antibodies are overlapping but not identical. Both factors are composed of two polypeptide chains, and both chains are required for suppressive activity; one chain bears the I-J determinant, whereas the other possesses the idiotype-binding activity of the intact molecule. Both idiotype-binding factors are restricted by MHC- and Igh-linked genes, and transcomplementation is observed in the F1 mice between MHC-congenic and Igh-congenic parents. Both factors are active late in Mishell-Dutton cultures. These data support the contention that these two factors are similar but nonidentical members of an anti-idiotypic class of GAT-specific suppressor factors.