title: Elevated and cross-responsive CD1a-reactive T cells in bee and wasp venom allergic individuals.
abstract: 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.
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine and University of Oxford, NIHR Biomedical Research Centre, Oxford, England, UK.
authors.forename: Sumithra
authors.initials: S
authors.lastname: Subramaniam
authors.affiliation: Section of Musculoskeletal Disease, University of Leeds, Leeds, UK.
authors.forename: Aamir
authors.initials: A
authors.lastname: Aslam
authors.affiliation: Department of Clinical Immunology, Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: Siraj A
authors.initials: SA
authors.lastname: Misbah
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine and University of Oxford, NIHR Biomedical Research Centre, Oxford, England, UK.
authors.forename: Mariolina
authors.initials: M
authors.lastname: Salio
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine and University of Oxford, NIHR Biomedical Research Centre, Oxford, England, UK.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cerundolo
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: D Branch
authors.initials: DB
authors.lastname: Moody
authors.affiliation: MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine and University of Oxford, NIHR Biomedical Research Centre, Oxford, England, UK.
authors.forename: Graham
authors.initials: G
authors.lastname: Ogg
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology; D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology; D001514:Bee Venoms / Q000009:adverse effects / Q000276:immunology*; D002469:Cell Separation; D003429:Cross Reactions; D003888:Desensitization, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007299:Insect Bites and Stings / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000276:immunology*; D014862:Wasp Venoms / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000485:Allergens; D018949:Antigens, CD1; D001514:Bee Venoms; C419393:CD1a antigen; D014862:Wasp Venoms
keywords: CD1a-reactive T cells; Immunotherapy; Phospholipase; Venom allergy