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

作者：Hsu Shih Chang; Tsai Tsung Hsien; Kawasaki Hirokazu; Chen Chien Ho; Plunkett Beverly; Lee Reiko T; Lee Yuan C; Huang Shau Ku^*

来源：Journal of Allergy and Clinical Immunology, 2007, 119(6): 1522-1528.

DOI：10.1016/j.jaci.2007.01.034

• dendritic cells
• C-type lectin receptor
• Lewis-x trisaccharides

Background: Glycoproteins containing Lewis-x (Le(x)) trisaccharides are often associated with the host's adaptive T(H)2-type immunity, but the mechanisms underlying the T(H)2-biased response are at present unclear.
Objective: The modulatory effect of Le(x) or its glycoconjugates on IgE/T(H)2 responses was investigated.
Methods: The levels of serum antibodies and cytokines were analyzed by means of ELISA, RT-PCR, or both.
Results: In C3H mice Le(x) coupled with BSA (Le(x)-BSA) elicited higher levels of specific IgE and IgG1, but not IgG2a, which were associated with increased levels of splenic T(H)2 cytokines when compared with those seen in BSA-sensitized mice. In BALB/c mice sensitized with Le(x)-BSA or Le(x) 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. Le(x) and an isomer, Le(y), but not other isomers, inhibited the production of LPS-induced IL-12p70, associated with a significant reduction of nuclear NF-kappa B, 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 Le(x) trisaccharides.
Conclusion: These results provide evidence for a potential role of Le(x) 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 Le(x) or similar oligosaccharides, including plant-derived (or food-derived) allergens, these findings might have a broad implication.
Clinical implications: The adjuvant activity of Le(x) trisaccharides might aid in vaccine design and might be important in determining the allergenicity of proteins containing this or other similar structures.

• 出版日期2007-6