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The role of CD1a-reactive T cells in human allergic disease is unknown. We have previously shown that circulating CD1a-reactive T cells recognize neolipid antigens generated by bee and wasp venom phospholipase, and here tested the hypothesis that venom-responsive CD1a-reactive T cells associate with venom allergy. Circulating T cells from bee and wasp venom allergic individuals, before and during immunotherapy, were exposed to CD1a-transfected K562 cells in the presence of wasp or bee venom. T-cell response was evaluated based on IFNγ, GM-CSF, and IL-13 cytokine production. Venom allergic individuals showed significantly higher frequencies of IFN-γ, GM-CSF, and IL-13 producing CD1a-reactive T cells responsive to venom and venom-derived phospholipase than healthy individuals. Venom-responsive CD1a-reactive T cells were cross-responsive between wasp and bee suggesting shared pathways of allergenicity. Frequencies of CD1a-reactive T cells were initially induced during subcutaneous immunotherapy, peaking by weeks 5, but then reduced despite escalation of antigen dose. Our current understanding of venom allergy and immunotherapy is largely based on peptide and protein-specific T cell and antibody responses. Here, we show that lipid antigens and CD1a-reactive T cells associate with the allergic response. These data have implications for mechanisms of allergy and approaches to immunotherapy.

Original publication

DOI

10.1002/eji.201545869

Type

Journal article

Journal

Eur J Immunol

Publication Date

01/2016

Volume

46

Pages

242 - 252

Keywords

CD1a-reactive T cells, Immunotherapy, Phospholipase, Venom allergy, Adult, Allergens, Animals, Antigens, CD1, Bee Venoms, Cell Separation, Cross Reactions, Desensitization, Immunologic, Enzyme-Linked Immunosorbent Assay, Enzyme-Linked Immunospot Assay, Female, Humans, Hypersensitivity, Insect Bites and Stings, Male, Middle Aged, T-Lymphocytes, Wasp Venoms