The ability of certain inbred mouse strains to produce high or low titers of IgE and IgG antibodies to limiting doses of antigen plus adjuvants is under genetic control. An important feature of the immune responses produced to these antigens is their strong dependence on interactions between T and B lymphocytes whose specificity is rigidly controlled by genes which map within the major histocompatibility complex region, probably because of the region's profound effects on cell plasma membrane receptor molecules. The production of IgE antibody is now known to be particularly sensitive to regulation by helper and suppressor T cells. As lymphoid cells have been shown to possess receptors to vasocative amines, this project considers the possibility that the antigen-induced release of mediators, principally histamine, from sensitized mast cells plays a role in the regulation of specific immune responses by modifying the interactions between the various lymphocyte classes which are mobilized during these events. Pertinent to these questions are the observations that apparently Ir-gene restricted non-responder mouse strains may produce high IgE titers when suppressor T cell activity is eliminated. Making use of histamine-affinity columns and cell transfer experiments, the principal investigator will attempt to identify the type or types of histamine receptor bearing lymphoid cells and cells and to assess the role that histamine induced changes in cyclic AMP metabolism plays in the inhibition of the response of specific immunocompetent cells to antigen. Such experiments should contribute to the understanding of the biological function of IgE outside of the pathogenesis of atopic diseases.