[Alterations in immunological responses: conformational changes of allergens and application to hyposensitivity...

To establish a novel strategy for allergen immunotherapy, human immunoresponses against conformational variants of a mite allergen were examined. Heat treatment of major house dust mite allergen, Der f2 caused molecular aggregation, while its ability to bind IgE remained unchanged. C8/119S, a mutant protein of Der f2 with the cysteine residues at positions 8 and 119 being replaced by serines, leads to degenerate secondary structure, molecular polymerization and Th1 cell differentiation. C8/119S also lost the ability to bind IgE. On the other hand, misfolded recombinant Der f2 also exhibits degenerate secondary structure, molecular polymerization and Th1 cell differentiation, however, its ability to bind IgE is retained. Loss of IgE binding ability and Th1 skewed immunogenicity of C8/119S are attributed to alterations in antigen-presenting cells and its cytokine profiles. These findings may lead to a novel allergen immunotherapy.