HLA-DQ6, -DQ8, -DR3, and -DR4 transgenic (tg) mice were studied to examine the role of human Class II molecules on the Y217L BPN' respiratory immune response. Y217L BPN' is an industrial enzyme and a known occupational allergen.

Mice were immunized with Y217L BPN' and several parameters were evaluated: 1) T cell epitopes 2) IgG1/IgE and 3) histological analysis of lung and BAL.

DQ8 mice were shown to be most susceptible to development of Th2 hypersensitivity to Y217L BPN' based on the development of significant levels of Ag-specific IgG1/IgE and eosinophilia after 5 immunizations. Several T cell epitopes were identified in DQ8 mice with major epitopes spanning 5 regions of the protein defined by amino acids 40-54, 73-90, 106-126, 184-213, and 238-255. Immunized DQ6 and DR3 mice exhibited low but detectable levels of Ag-specific IgG1/IgE but no eosinophilia or significant proliferative responses to synthetic peptides (T cell epitopes). This suggested that the time to peak Ab production and T cell proliferation may be longer in DQ6 and DR3 mice. Therefore, longer term repeated exposure to the enzyme in DQ6 mice was undertaken. With additional immunizations, DQ6 mice generated a robust IgG1 response. In addition, 3 major T cell epitope regions were identified and were similar to those seen in DQ8 mice: 67-87, 109-123 and 184-204.

HLA Class II molecules are important in development of IgG1/IgE and eosinophilia to Y217L BPN'. We propose that HLA Class II tg mice should be studied further as models to understand the allergic response to enzymes.