Through Objective #3, we will seek to understand the molecular processes by which walnut OIT affects the immune system through evaluation of immune mechanisms in relationship to clinical findings of desensitization and/or tolerance. We will delineate the impact of walnut OIT on the subsequent cellular and humoral response to walnut protein by the following: 1) analysis of walnut and second tree nut specific IgE, IgG and IgG4 response, 2) characterization of allergen specific basophil activation, 3) characterization of mast cell responses through skin prick testing, and 4) analysis of specific T cell cytokine responses and regulatory T cell activation. We anticipate that the effect of walnut OIT will occur either by induction of regulatory T cells, conversion of T cells from an allergic (Th2) to a non-allergic (Th1) lymphocyte response (measured by cytokines, antibody levels, and skin prick test size), or a change in walnut-specific basophil activation.