2. Academic Validation
  3. Bee venom processes human skin lipids for presentation by CD1a

Bee venom processes human skin lipids for presentation by CD1a

  • J Exp Med. 2015 Feb 9;212(2):149-63. doi: 10.1084/jem.20141505.
Elvire A Bourgeois 1,  Sumithra Subramaniam 2,  Tan-Yun Cheng 1,  Annemieke De Jong 1,  Emilie Layre 1,  Dalam Ly 1,  Maryam Salimi 2,  Annaliza Legaspi 3,  Robert L Modlin 3,  Mariolina Salio 2,  Vincenzo Cerundolo 2,  D Branch Moody 4,  Graham Ogg 5
Affiliations

Affiliations

  • 1 Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02114.
  • 2 MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine and University of Oxford NIHR Biomedical Research Centre, Oxford, Oxfordshire OX3 9DS, England, UK MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine and University of Oxford NIHR Biomedical Research Centre, Oxford, Oxfordshire OX3 9DS, England, UK.
  • 3 Division of Dermatology, David Geffen School of Medicine, Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095 Division of Dermatology, David Geffen School of Medicine, Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA 90095.
  • 4 Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02114 bmoody@partners.org graham.ogg@ndm.ox.ac.uk.
  • 5 MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine and University of Oxford NIHR Biomedical Research Centre, Oxford, Oxfordshire OX3 9DS, England, UK MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine and University of Oxford NIHR Biomedical Research Centre, Oxford, Oxfordshire OX3 9DS, England, UK bmoody@partners.org graham.ogg@ndm.ox.ac.uk.
PMID: 25584012 DOI: 10.1084/jem.20141505
Abstract

Venoms frequently co-opt host immune responses, so study of their mode of action can provide insight into novel inflammatory pathways. Using bee and wasp venom responses as a model system, we investigated whether venoms contain CD1-presented antigens. Here, we show that venoms activate human T cells via CD1a proteins. Whereas CD1 proteins typically present lipids, chromatographic separation of venoms unexpectedly showed that stimulatory factors partition into protein-containing fractions. This finding was explained by demonstrating that bee venom-derived Phospholipase A2 (PLA2) activates T cells through generation of small neoantigens, such as free fatty acids and lysophospholipids, from common phosphodiacylglycerides. 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.

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