Dominant, non-MHC genetic control of food allergy in an adjuvant-free mouse model

Food allergy is a potentially fatal immune-mediated disorder with incompletely understood mechanisms. We studied the genetic control of food allergy using major histocompatibility complex-identical mice (H2(s)) and an adjuvant-free method of sensitization. Whereas, transdermal exposure to hazelnut - a model allergenic food, elicited robust IgG1 response in both strains, an IgE response was evident only in A.SW mice. Following oral challenge, only A.SW but not SJL mice exhibited signs of systemic anaphylaxis and hypothermia. In addition, (A.SW x SJL) F1 hybrids exhibited IgE responsiveness, systemic anaphylaxis and hypothermia similar to A.SW, indicating dominant inheritance of these traits. Furthermore, whereas A.SW and F1 mice but not SJL elicited robust interleukin (IL)-4 response, all three strains elicited IL-5 and IL-13 responses by spleen cells. These data demonstrate for the first time, dominant non-MHC genetic control of food allergy and a critical role of IL-4 but not IL-5 or IL-13 in this model.