REGULATION OF REAGINIC ANTIBODY RESPONSE

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The purpose of this research is to find some maneuvers to suppress the IgE antibody response to allergen in an antigen-specific manner. Previous studies have shown that a lipomodulin-like lymphokine, i.e., glycosylation inhibiting factor (GIF), facilitated the generation of antigen-specific suppressor T cells (Ts), which form their own GIF. Upon antigenic stimulation, the antigen-specific Ts form GIF that has affinity for nominal antigen. The antigen-binding GIF appears to be identical to antigen- specific Ts factor (TsF), and composed of antigen-binding chain and nonspecific GIF. Based on the findings, we established an immmunological maneuver to construct Ts hybridomas from antigen-primed murine spleen cells, and demonstrated that antigen-binding GIF from the hybridomas suppressed the antibody response of the donor of the spleen cells to homologous antigen. As the results of application of the same method to peripheral blood mononuclear cells of a patient, allergic to bee venom, we established human T cell hybridomas which produce antigen-binding GIF upon cross-linking of CD3 on the cells. Since murine GIF was isolated to biochemical homogeneity, i) attempts will be made to isolate human nonspecific GIF, and to biochemically characterize antigen-binding GIF of both species. ii) Based on the structure of murine nonspecific GIF, CDNA clone encoding the lymphokine will be isolated, and the experiments will be extended to obtain CDNA encoding human GIF. iii) We shall test the hypothesis that antigen-binding GIF as well as T cell receptors of the cell source of the factor recognize a common epitope representing an external structure in the antigen molecule, and that a certain epitope specificity of the lymphokine is essential for immunosuppressive effects. iv) Finally, mechanisms of immunosuppression by GIF will be investigated in murine system. Since our recent studies indicated that GIF suppresses presentation of antigen by splenic adherent cells to T cells, the effect of antigen-binding GIF on antigen-presenting cells will be analyzed.