Lipid-specific T cells and the skin

Langerhans cells express constitutively high levels of CD1a, a member of the CD1 family of molecules which are known to present lipid antigens to T cells. Whilst much human skin immunology research has focussed on the function of T cells which recognise peptides presented by HLA molecules, in contrast few studies have addressed the role of CD1a and lipid antigens in the pathogenesis of inflammatory skin disease. House dust mite and bee and wasp venom extracts were found to generate CD1a reactivity, but paradoxically this function was within the protein and not lipid fraction. This unexpected finding was explained by the presence of phospholipases within the house dust mite and insect venoms which generated antigenic lipids on contact with skin. The lipids then bind to CD1a on Langerhans cells which are recognised by T cells, which in turn contribute to skin inflammation. This newly identified pathway of skin inflammation defines several potential points for therapeutic intervention.