Dust mite allergens have been shown to play a major role in both asthma and atopic dermatitis. The long-term objective of this proposal is to combine the strengths of two groups of investigators to investigate the cellular basis of human allergic response to house dust mite allergens. One of these groups is interested in the epidemiology and the structure of relevant allergens in house dust mite induced allergy while the other is interested in the cellular basis of the human immune response. Three groups: patients with atopic dermatitis, patients with asthma and normal household members or age-matched controls will be studied. The allergen, Der p II will be used as a representative Group II allergen of the house dust mite. It is intended to generate monoclonal T and B cell lines to determine both T and B epitopes on the group II allergen and to ascertain whether there are differences between these groups. Experiments are designed to test the hypothesis that the allergic response is correlated with the host tendency to mount a T cell response with dominant IL-4 expression, i.e., the Th 2 response.
Five specific aims are proposed: (1) To generate human IgE secreting monoclonal hybridomas to provide reagents to map the B cell epitopes on Der p II as proposed in project 1 in the center grant; (2) To determine the V gene usage by these well defined monoclonal antibodies; (3) To determine the cytokine expression patterns of T cells responsive to Der p II in vitro, with special emphasis on the role of added cytokines and the CD4O interaction with its ligand: (4) To establish Der p II specific T cell clones, to use them to map the T cell epitopes on this allergen and to determine the V gene usage by the clones and (5) To study cytokine expression by infiltrating T cells in the skin lesion induced by the patch test with Der p II and to establish antigen-specific T cell clones from the infiltrating T cells. The results from these experiments will provide further information on the cellular basis of the human allergic response to house dust mite allergens and may provide rationales for novel therapeutic interventions in these important allergic diseases.
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