Heterogeneous responses and cross reactivity between the major peanut allergens Ara h 1, 2,3 and 6 in a mouse model for peanut allergy (1)
Sensitization to peanut is characterized by the presence of IgE to a number of peanut allergens. Up till now, thirteen peanut allergens, designated Ara h 1–13, are recognized by the WHO/IUS allergen nomenclature subcommittee. Cross reactivity between peanut proteins and tree nut proteins and other allergens are common, even among different protein families.
Sensitization with the individual peanut proteins led to the induction of IgE antibody responses with specificity to the allergen used. In addition, extensive cross reactivity was observed between peanut proteins, since Ara h 1, 2, 3 and 6 specific IgE antibodies were detected in all sensitized groups.
Sensitization with PE, followed by restimulation with PE, Ara h 1, 2, 3, or 6 led to induction of the Th2 cytokines IL‐5, IL‐13. PE restimulation of spleens derived from Ara h 1, 3, or 6 sensitized mice induced the same cytokine response. Restimulation with Ara h 2, however, led to lower Th2 cytokine responses in all groups. Restimulation with the individual peanut proteins led to the induction of Th2 responses not only in mice of the same sensitizing allergen, but also in mice sensitized with one of the other peanut allergens. This cross reactivity was observed in Ara h 1, 3 and 6 sensitized mice for both IL‐5 and IL‐13.
Mucosal mast cell degranulation was measured after intra‐gastric challenge with PE, Ara h 1, 2, 3 and 6 in correspondingly sensitized mice by measuring mMCP‐1 and histamine in plasma. Interestingly, only PE, Ara h 2 and 6 were able to induce mucosal mast cell degranulation and histamine release in sensitized mice.
Despite the sensitizing capacity of Ara h 1, 2, 3 and 6, only Ara h 2 and 6 were able to elicit mast cell degranulation after intra‐gastric challenge. Ara h 6, which is 60% homologous to Ara h 2 was able to stimulate T cells in our and the human studies. Since mice and human do develop T cell‐dependent IgE responses to Ara h 2 in vivo, the lack of T cell stimulation by Ara h 2 may be caused by the high stability and lack of degradation of this protein by DC in vitro.