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
Related in: MedlinePlus
License 1 - License 2
Mentions: To directly test the hypothesis that bee venom PLA2 acts by cleaving intact cellular phospholipids to create neoantigens, we preincubated the enzyme with two synthetic substrates for bee venom PLA2, phosphatidylcholine comprised of singly unsaturated C18 fatty acyl chains (PC 18:1/18:1) and phosphatidic acid with C16 fatty acyl chain in sn-1 and unsaturated C18 fatty acyl chain in sn-2 (PA 16:0/18:1). We also tested for a T cell response to products of cleavage by PLA2 and control lipids (Fig. 5 A), including purified free fatty acids and lysophospholipids: lysophosphatidylcholine (LPC 18:1), oleic acid (FA 18:1), lysophosphatidic acid (LPA 18:1), and palmitic acid (FA 16:0). Higher production of IFN-γ was obtained in response to phospholipids when preincubated with PLA2. BC2 T cells responded to fatty acids to a greater extent than intact phospholipids or lysophospholipids. This result suggests that PLA2 activates CD1a-restricted T cells by cleaving nonantigenic phospholipids into lysophospholipids and antigenic fatty acid, in agreement with a recent study identifying free fatty acids as CD1-presented antigens (de Jong et al., 2014).
Affiliation: Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02114.