Bee venom processes human skin lipids for presentation by CD1a.
Bottom Line: Patient studies showed that injected PLA2 generates lysophospholipids within human skin in vivo, and polyclonal T cell responses are dependent on CD1a protein and PLA2.These findings support a previously unknown skin immune response based on T cell recognition of CD1a proteins and lipid neoantigen generated in vivo by phospholipases.The findings have implications for skin barrier sensing by T cells and mechanisms underlying phospholipase-dependent inflammatory skin disease.
Affiliation: Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02114.Show MeSH
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Mentions: Having identified PLA2 as sufficient to generate CD1a-presented antigens in vitro using T cell clones, we next sought to determine if bee venom PLA2 is sufficient to activate polyclonal T cells ex vivo in cellular assays (Fig. 7). As with whole venoms (Fig. 1), we detected higher IFN-γ–producing cells with the addition of 100 ng/ml bee venom PLA2 but only in the presence of CD1a and not other CD1 isoforms (Fig. 7 A, left). We observed significantly (P < 0.001) higher CD1a-restricted responses in the presence of PLA2 in a cohort of 18 donors (Fig. 7 A, right). More detailed testing of an individual responder showed that anti-CD1a antibodies prevented the response to CD1a and PLA2 (P < 0.05), confirming the essential role of CD1a (Fig. 7 B, left).
Affiliation: Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02114.