The requirements for growing and propagating antigen-specific and idiotype-specific suppressor T cells will be studied, with the aim of developing a reproducible cloning strategy. In order to accomplish this, the response will be initiated with Ts-inducing determinants and appropriate specific accessory inducer cells, as well as driving the response (a) by using conjugates of mitogens and specific ligands, or (b) performing cyclic enrichment (specific selection and nonspecific stimulation) and by using combinations of special growth factors. Recent evidence points to the reactivity of regulatory cells with the recognition structures on MHC-restricted T cells. This T-T network and especially, the specificity of its idiotypic interaction, will be the focus of these studies. The development of such regulatory cells in fetal thymic lobe cultures will be studied and intercellular restrictions between closely related strains (B6 and its Ia mutant strain, bm12) will be examined. The study of tolerance induced by immunogenic or suppressogenic determinants will be completed and the contributions of clonal inactivation vs. suppressive cell involvement in tolerance induction will be detailed. Further, the induction of tolerance in various regulatory subpopulations of T cells will be investigated among antigen-specific and idiotype- specific sets. In the lysozyme and beta-galactosidase systems, small peptide are known to induce suppression. These """"""""suppressor determinants"""""""" (SD) will be studied in detail to determine each essential residue and whether it is required for T suppressor cell binding (or is related to MHC function); also, it can be asked whether certain """"""""Th"""""""" cells have a suppressive phenotype. To investigate the mechanism of Ts action, """"""""grafts"""""""" of an SD onto an immunogenic peptide will be made and the requirements for this antigen-bridging suppression studied. A model peptide containing a Ts-inducing determinant, a Th-inducing determinant and a B cell determinant will be utilized to study the positional and specificity requirements associated with cell interaction. The interrelations of the different predominant idiotypes of the primary and secondary antibody responses to lysozyme will be studied.
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