Two groups of experiments are planned. These problems are interconnected as both concern the murine IgE molecule. The first goal of this proposal is to continue studies of the production of anti-dinitrophenyl (DNP) IgE antibody and the influence of interleukins, especially IL-4, on the switch from IgM production to anti-DNP IgE production. Most of the previous work, published by several authors, investigated the switch from """"""""normal"""""""" polyclonal immunoglobulins of the IgM or IgG classes to polyclonal """"""""normal"""""""" IgE. The word """"""""normal"""""""" underlines that fact that the specificity of the immunoglobulins, the antigen with which they react, is unknown. Two T helper cell clones (L3T4) will be used. These clones are specific for keyhole limpet hemocyanin (KLH) and both were already investigated using B cells primed for anti-DNP antibody production. The production of anti-DNP IgM and IgG were both investigated, but not the production of anti-DNP IgE. These clones will be used together with B cells from mice syngeneic to the T cell clones. The influence of recombinant interleukins rIL-4 and rIL-2, and the influence of monoclonal anti-IL-4 and anti-IL-2 on anti-DNP IgE production will be investigated. The second goal is to study the in vitro suppression of IgE antibody specific for the DNP (dinitrophenyl) hapten. Using adoptive transfer, the applicant has demonstrated that in the SJL strain of mice, suppression of IgE antibody against DNP can be obtained. Mice primed with DNP-protein and given T cells from other mice that have been hyperprimed with an unrelated carrier protein suppress anti-DNP IgE production if this second carrier is injected. Dr. Ovary proposes to study this suppression in vitro and then instead of using hyperprimed spleen cells (plus antigen) study the possible suppressive affects in this system of different lymphokines. If successful, he proposes to use the system described above (first goal) to examine suppression of antigen specific IgE when well-defined cloned T cells are used as helper cells.
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