Contribution of conformational stability of hen lysozyme to induction of type 2 T-helper immune responses.
It is important to identify characteristics that confer on proteins the potential to induce allergenic sensitization and allergenic disease. Protein allergens carry T-cell epitopes that are capable of inducing a type 2 T helper (Th2) cell response. There is limited information regarding factors that govern the allergenicity of proteins. We previously reported that a decrease in the conformational stability of hen-egg lysozyme (HEL) enhanced its capacity to activate HEL-specific T cells owing to the increased susceptibility to intracellular antigen processing. To determine whether the conformational stability of HEL makes for a critical contribution to allergenic sensitization in vivo, we immunized BALB/c mice with HEL derivatives of different conformational stability, but which retained a similar three-dimensional structure. The magnitude of in vivo T-cell responses, evaluated by ex vivo proliferative responses of lymph node T cells from mice primed with various HEL derivatives, was inversely correlated with conformational stability, as was interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production by splenic T cells in response to HEL. Immunization of the least stable derivative led to a potent IL-4 response and to immunoglobulin E (IgE) antibody production. We propose that the intrinsic allergenicity of proteins can be determined by the degree of conformational stability.
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Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Ito
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Hirata
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Ueda
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Imoto
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D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D009113:Muramidase / Q000737:chemistry / Q000276:immunology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000941:Antigens; D018984:Epitopes, T-Lymphocyte; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; C421864:hen egg lysozyme; D009113:Muramidase