Oral exposure to food allergens may be limited in infancy, and the initial site of antigen exposure likely plays an important role in food allergy induction.

To examine the impact of different routes of exposure by using milk allergens, with and without adjuvant, on sensitization.

C3H/HeJ mice were repeatedly exposed to the milk allergen ⍺-lactalbumin (ALA), with or without cholera toxin (CT). Sensitization routes used were intragastric, cutaneous, intranasal, and sublingual. Anaphylaxis severity was assessed by symptoms and body temperature in response to oral challenge. Antigen-specific serum antibodies were measured by ELISA. The mechanism of adjuvant activity of cutaneous CT was also determined.

Sensitization to ALA as measured by allergen-specific IgE occurred by all routes of sensitization and was maximal in response to cutaneous exposure. Sensitization was dependent on CT and did not occur to antigen alone by any route. Mucosal, but not cutaneous, exposure resulted in a robust allergen-specific IgA response. Anaphylaxis occurred in all sensitized groups when orally challenged with ALA. Topical CT induced migration of langerin^neg dermal dendritic cells to the lymph node, resulting in enhanced proliferation and T_H2 cytokine production from responder T cells.

Sensitization can occur via all physiologic routes when adjuvant is present. The skin is a potent and likely important physiologic route of sensitization whereby adjuvant induces an efflux of antigen-bearing dermal dendritic cells to the lymph node that generate a proallergic T_H2 response.