Interleukin-2 binds to gangliosides in micelles and lipid bilayers

Gangliosides shed from the surface of tumour cells may be involved in tumour-induced immunosuppression. These anionic sialoglycolipids are known to be potent inhibitors of lymphocyte proliferation, and it has been suggested that they interfere with processes mediated by the growth factor interleukin-2 (IL-2). We have thus investigated the interaction of IL-2 with gangliosides in micelles and lipid bilayers. Gel filtration FPLC showed that 125I-IL-2 can bind to micellar gangliosides in aqueous solution, and this interaction was strongly promoted by low concentrations of serum. Binding to ganglioside micelles was specific in that it required a native IL-2 molecule. IL-2 binding remained unchanged in the presence of 40% ethylene glycol, suggesting that it was not due to hydrophobic interactions. Ganglioside oligosaccharides alone were not able to bind to IL-2. Direct binding studies and gel filtration chromatography indicated that both multilamellar liposomes and 100 nm unilamellar vesicles containing gangliosides were able to interact with IL-2. Bilayers of lipid alone showed no binding. The interaction of IL-2 with bilayer gangliosides was highly dependent on the bilayer lipid composition, but appeared independent of lipid phase state. These results suggest that gangliosides may be a physiologically relevant target for IL-2 binding.