Human in vitro experimental model for CD4+ T cell targeted immunotherapy to house dust mite

CD4+ T cells play a critical role in the initiation and potentiation of the allergic immune response. Development of allergen-mediated hyposensitization therapies directed at this cell type requires two key steps: (1) identification of the epitopes that are crucial for activating the T-cell response and (2) definition of the specificity of the HLA-D region molecules that restrict T-cell recognition of these epitopes. We have located the major T-cell determinants of the group II allergen of the house dust mite species Dermatophagoides pteronyssinus (Der p II). We have also identified a T-cell clone for which the HLA-DP*0401 allele restricts recognition of the group I allergen residues of house dust mite. This clone overproduces IL-4 and IL-5, cytokines that promote IgE synthesis. When these cells are rendered nonresponsive by incubation with a supraoptimal concentration of their allergen peptide determinant, they lose their ability to secrete IL-4 but maintain interferon gamma production. This modified pattern favors a switch away from the pathway of IgE synthesis to that of IgG synthesis. These findings suggest that the use of selected peptides in vaccines may allow the redirection of allergic immune responses.