Due to IgE cross-reactivity, birch pollen-allergic individuals frequently develop type I hypersensitivity reactions to celery tuber. We evaluated the T cell response to the major allergen in celeriac, Api g 1, and the cellular cross-reactivity with its homologous major allergen in birch pollen, Bet v 1. Api g 1-specific T cell lines (TCL) and clones (TCC) were established from peripheral blood mononuclear cells of allergic patients. Epitope mapping of Api g 1 with overlapping Api g 1-derived peptides revealed one dominant T cell-activating region, Api g 1(109-126). TCL and TCC generated with Api g 1 cross-reacted with the birch pollen allergen and, although initially stimulated with the food allergen, cellular responses to Bet v 1 were stronger than to Api g 1. Epitope mapping with Bet v 1-derived peptides revealed that T cells specific for several distinct epitopes distributed over the complete Bet v 1 molecule could be activated by Api g 1. Bet v 1(109-126) was identified as the most important T cell epitope for cross-reactivity with Api g 1. This epitope shares 72% amino acid sequence similarity with the major T cell-activating region of the food allergen, Api g 1(109-126). Our data provide evidence that humoral as well as cellular reactivity to the major celery allergen is predominantly based on cross-reactivity with the major birch pollen allergen. The activation of Bet v 1-specific Th2 cells by Api g 1, in particular outside the pollen season, may have consequences for birch pollen-allergic individuals.