Crystal structure of Urtica dioica agglutinin, a superantigen presented byMHC molecules of class I and class II

Background: Urtica dioica agglutinin (UDA), a monomeric lectin extracted fr om stinging nettle rhizomes, is specific for saccharides containing N-acety lglucosamine (GlcNAc). The lectin behaves as a superantigen for murine T ce lls, inducing the exclusive proliferation of V beta 8.3(+) lymphocytes, UDA is unique among known T cell superantigens because it can be presented by major histocompatibility complex (MHC) molecules of both class I and II. Results: The crystal structure of UDA has been determined in the ligand-fre e state, and in complex with tri-acetylchitotriose and tetra-acetylchitotet raose at 1.66 Angstrom, 1.90 Angstrom and 1.40 Angstrom resolution, respect ively. UDA comprises two hevein-like domains, each with a saccharide-bindin g site. A serine and three aromatic residues at each site form the principa l contacts with the ligand. The N-terminal domain binding site can centre o n any residue of a chito-oligosaccharide, whereas that of the C-terminal do main is specific for residues at the nonreducing terminus of the ligand. We have shown previously that oligomers of GlcNAc inhibit the superantigenic activity of UDA and that the lectin binds to glycans on the MHC molecule. W e show that UDA also binds to glycans an the T cell receptor (TCR). Conclusions: The presence of two saccharide-binding sites observed in the s tructure of UDA suggests that its superantigenic properties arise from the simultaneous fixation of glycans on the TCR and MHC molecules of the T cell and antigen-presenting cell, respectively. The well defined spacing betwee n the two binding sites of UDA is probably a key factor in determining the specificity for V beta 8.3(+) lymphocytes.