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Bee venom processes human skin lipids for presentation by CD1a.

Elvire A Bourgeois1, Sumithra Subramaniam2, Tan-Yun Cheng1

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Bee and wasp venoms activate human T cells via CD1a proteins by generating lipid neoantigens. This reveals a novel skin immune response involving phospholipase A2 (PLA2) and T cell recognition.

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Area of Science:

  • Immunology
  • Biochemistry

Background:

  • Venoms often manipulate host immune responses, offering insights into inflammatory pathways.
  • CD1 proteins are known to present lipid antigens to T cells.

Purpose of the Study:

  • To investigate if venoms contain CD1-presented antigens.
  • To explore the mechanism by which venoms activate T cells.

Main Methods:

  • Chromatographic separation of venom components.
  • In vitro T cell activation assays.
  • In vivo studies using patient skin and phospholipase A2 (PLA2) injection.

Main Results:

  • Venoms activate human T cells through CD1a proteins.
  • Stimulatory factors in venoms were found in protein-containing fractions, not lipid fractions.
  • Bee venom-derived phospholipase A2 (PLA2) generates neoantigens (fatty acids, lysophospholipids) from phosphodiacylglycerides, activating T cells.
  • PLA2 injection in patients generates lysophospholipids in skin, driving CD1a-dependent T cell responses.

Conclusions:

  • A novel skin immune response exists, mediated by T cell recognition of CD1a proteins and in vivo generated lipid neoantigens by phospholipases.
  • This discovery has implications for understanding T cell sensing of the skin barrier and inflammatory skin diseases driven by phospholipases.