This project deals with IgE-mediated human allergic responses to mouse urinary protein (MUP) which is a major human allergen. SUB- PROJECT ONE: IMMUNOREGULATION WITH DEFINED MOUSE ALLERGEN. The extensive knowledge of the genetics and structure of MUP and the closely related rat alpha2 euglobulin (a2Ug) will be exploited to further knowledge of mechanisms and immunotherapy in human IgE mediated allergy. It will be demonstrated that epitopes that are presented to T cells and that bind to IgE antibody are widely shared in this complex family of proteins. Immunoreactive fragments of MUP will be selected, synthesized and screened for immunoregulatory potential (inhibition of T cell activation at the antigen presentation level, generation of supressor T cells, inhibition of in vitro IgE antibody synthesis). These fragments will be tested for binding to IgE antibody and in vivo activity (skin test and bronchial reactivity). Double-blind trials will then be set up to test these fragments for efficacy in the immunotherapy of human occupational allergy to mice. IgE and IgG antibody responses, generation of supressor T cells, skin test and bronchial reactivity and clinical scores will be used to evaluate response. SUB-PROJECT TWO: IMMUNOLOGY AND EPIDEMIOLOGY OF OCCUPATIONAL ALLERGY TO MICE. IgE antibody binding will be tested in a selected population of workers to verify the importance of MUP in human allergy. This will be followed by a cross-sectional survey of existing employees for the presence and severity of allergy and levels of IgG and IgE antibody to MUP and other minor allergens such as albumin. All new workers who are hired will be studied prospectively for factors that will predict allergy. HLA typing will establish a link between IgE antibody and immune response genes. Systematic sampling of air and dust in various work locations will be correlated with such factors as ventilation rates, filter systems and types of caging. The level of allergen in the air will be compared with worker's allergic symptoms and the results of bronchial challenge with MUP.
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