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.