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

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.