Vicilin and 11s globulin cashew allergens share promiscous CD4+ T cell epitopes with other tree nuts (APP2P.100)

Allergic reactions to cashew can be life threatening. While IgE-specific cashew epitopes have been studied, CD4+ T-cell specific epitopes for cashew remain uncharacterized. Additionally, cross-reactivity amongst tree nuts has not been examined in humans at the T-cell level. We sought to provide a thorough phenotypic analysis of cashew reactive T-cells in allergic and non-allergic subjects as well as to identify promiscuous epitopes among tree nut allergens. CD4+ T-cell responses by CD154 up-regulation assays indicate that cashew allergens Ana o 1 and Ana o 2 play a major role in cashew allergy. Multiple Ana o 1 and Ana o 2 T-cell epitopes were identified with the Tetramer-Guided Epitope Mapping approach. Direct ex vivo staining showed that the majority of Ana o 1 and Ana o 2-specific T-cells have a CCR4+ TCM (central memory) phenotype while a subset of these T-cells express CCR4+CCR6+ in allergic subjects. Conversely, in non-allergic subjects a CXCR3+ population was observed. Cashew-specific T-cell clones for several epitope regions responded robustly to hazelnut and pistachio but not to walnut, while some epitopes responded to cashew exclusively and were found to be species specific. Allergic responses to cashew could be triggered by cross-reactive tree nut epitopes, therefore, restricted consumption of tree nuts should be advised for cashew allergic subjects.