Contribution of conformational stability of hen lysozyme to induction of type 2 T‐helper immune responses

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Abstract
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‐γ (IFN‐γ) 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.