A method was developed for the determination of putative lectin activities of cytokines. It involved the immunoblotting measurement of the quantity of these cytokines unbound to a series of different immobilized glycoconjugates and displacement of the bound cytokines with oligosaccharides of known structures. This method allows demonstrating that the following interleukins specifically recognize different oligosaccharide structures in a calcium-independent mechanism: interleukin-1␣ binds to the biantennary disialylated N-glycan completed with two Neu5Ac␣2-3 residues; interleukin-1 to a GM 4 sialylated glycolipid Neu5Ac␣2-3Gal1-Cer having very long and unusual long-chain bases; interleukin-4 to the 1,7 intramolecular lactone of N-acetyl-neuraminic acid; interleukin-6 to compounds having N-linked and O-linked HNK-1-like epitopes; and interleukin-7 to the sialyl-Tn antigen. Because the glycan ligands are rare structures in human circulating cells, it is suggested that such activities could be essential for providing specific signaling systems to cells having both the receptors and the oligosaccharide ligands of the interleukin at their cell surface.Cytokines are modulators of the activity of the immune system, their mechanism of action remaining, for the most part, not decrypted. As a general rule, the action of a cytokine results from its binding to membrane receptors, a series of molecules coupled to signaling systems involving kinases and/or phosphatases (1-5). The binding of a cytokine to its receptor(s) generally results in the phosphorylation/dephosphorylation of the intracytoplasmic domain of the receptor(s), the first step of the signaling. In general, the phosphorylation/dephosphorylation mechanism is cell type-specific, the kinases/phosphatases involved in these processes being quite specifically associated with surface molecular complexes different from the cytokine receptor complex (3, 6). Even when two different cytokines use the same receptor, the signal transduction pathways may be specific of the cytokines (7).We made the hypothesis that the specific association of interleukin receptors with other surface complexes could be due to carbohydrate-binding properties of these cytokines, a property already suggested in the literature (8 -14). The lectin activity of interleukin-2 (IL-2) 1 for specific oligomannosides (15) appeared to be essential, because IL-2 behaves as a bifunctional molecule able to extracellularly associate its  receptor (IL-2R) to other surface receptor complexes bearing N-glycans recognized by IL-2. This is the case for the CD3⅐TCR complex in which a N-glycosylated form of CD3 is an IL-2 ligand. This specific extracellular association is responsible for the specific phosphorylation of the IL-2R by the CD3⅐TCR-associated kinase p56 lck (15), considered as a first step in the antigenspecific activation process of CD4 ϩ T cells. As a consequence of this carbohydrate-binding property, it was suggested that oligomannosides accumulated in specific diseases or bound to specific microor...