Antigen coupled with Lewis-x trisaccharides elicits potent immune responses in mice

BackgroundGlycoproteins containing Lewis-x (Lex) trisaccharides are often associated with the host's adaptive TH2-type immunity, but the mechanisms underlying the TH2-biased response are at present unclear.ObjectiveThe modulatory effect of Lex or its glycoconjugates on IgE/TH2 responses was investigated.MethodsThe levels of serum antibodies and cytokines were analyzed by means of ELISA, RT-PCR, or both.ResultsIn C3H mice Lex coupled with BSA (Lex-BSA) elicited higher levels of specific IgE and IgG1, but not IgG2a, which were associated with increased levels of splenic TH2 cytokines when compared with those seen in BSA-sensitized mice. In BALB/c mice sensitized with Lex-BSA or Lex mixed with ovalbumin, significantly increased levels of specific IgE and IgG2a antibodies were found concomitant with reduced levels of serum IL-12p70. These effects were attenuated in IL-12–deficient BALB/c mice. Lex and an isomer, Ley, but not other isomers, inhibited the production of LPS-induced IL-12p70, associated with a significant reduction of nuclear NF-κB, in bone marrow–derived dendritic cells from BALB/c mice, suggesting that Lex-induced suppression of IL-12p70 results in an enhanced TH2 response. The addition of mannan, a known ligand for dendritic cell–specific intercellular adhesion molecule 3–grabbing nonintegrin, abrogated the suppressive effect of Lex trisaccharides.ConclusionThese results provide evidence for a potential role of Lex trisaccharides in shaping the immune responses through, at least in part, its suppressive effect on IL-12p70 production. Considering the relative ubiquity of glycoproteins with Lex or similar oligosaccharides, including plant-derived (or food-derived) allergens, these findings might have a broad implication.Clinical implicationsThe adjuvant activity of Lex trisaccharides might aid in vaccine design and might be important in determining the allergenicity of proteins containing this or other similar structures.