Airway dendritic cells (red) capture lipids from pollen grains (green) and present them on MHC CD1 molecules to lipid-reactive T cells.

On page 295, Agea and colleagues show that airway dendritic cells (DCs) help trigger allergic responses by capturing phospholipids from the surface of pollen grains and presenting them to lipid-reactive T cells. This is the first report of human T cells that recognize lipids derived from an environmental allergen. Thus, according to senior author Fabrizio Spinozzi, “the concept of the allergen should be extended to all pollen membrane structures,” not just proteins.T cell responses to allergens have traditionally focused on CD4+ T helper 2 (Th2) cells, which recognize peptides derived from protein allergens. Generating Th2 responses, however, requires the time-consuming processes of antigen processing and presentation, whereas allergic T cell responses develop very rapidly. Spinozzi thus suspected that something faster was at work.

Spinozzi's group now shows that phospholipids present on the surface of pollen grains bind to CD1 molecules on airway DCs, which then trigger lipid-reactive T cells to proliferate and produce cytokines. DCs that had been chemically fixed could still stimulate T cells, suggesting that the lipids could be captured directly from the pollen grains and did not require processing by the DC.

These lipid-specific T cells were most prevalent during allergy season and were rarely found in nonallergic individuals. In addition, greater numbers of CD1-expressing DCs were found in the airways of allergic individuals, which may help explain why nonallergic people don't respond to pollen-derived lipids in the same way.