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

Shih Chang Hsu, Tsung-Hsien Tsai, Hirokazu Kawasaki, Chien Ho Chen, Beverly Plunkett, Reiko T. Lee, Yuan C. Lee, Shau Ku Huang

Research output: Contribution to journalArticle

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Abstract

Background: Glycoproteins 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. Objective: The modulatory effect of Lex or its glycoconjugates on IgE/TH2 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 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. Conclusion: These 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 implications: The 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.

Original languageEnglish
Pages (from-to)1522-1528
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume119
Issue number6
DOIs
Publication statusPublished - Jun 2007

Fingerprint

Trisaccharides
Immunoglobulin E
Antigens
Dendritic Cells
Glycoproteins
Cytokines
Mannans
Glycoconjugates
Inbred C3H Mouse
Antibodies
Ovalbumin
Cell Adhesion Molecules
Adaptive Immunity
Interleukin-12
Serum
Oligosaccharides
Allergens
Vaccines
Immunoglobulin G
Bone Marrow

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Antigen coupled with Lewis-x trisaccharides elicits potent immune responses in mice. / Hsu, Shih Chang; Tsai, Tsung-Hsien; Kawasaki, Hirokazu; Chen, Chien Ho; Plunkett, Beverly; Lee, Reiko T.; Lee, Yuan C.; Huang, Shau Ku.

In: Journal of Allergy and Clinical Immunology, Vol. 119, No. 6, 06.2007, p. 1522-1528.

Research output: Contribution to journalArticle

Hsu, Shih Chang ; Tsai, Tsung-Hsien ; Kawasaki, Hirokazu ; Chen, Chien Ho ; Plunkett, Beverly ; Lee, Reiko T. ; Lee, Yuan C. ; Huang, Shau Ku. / Antigen coupled with Lewis-x trisaccharides elicits potent immune responses in mice. In: Journal of Allergy and Clinical Immunology. 2007 ; Vol. 119, No. 6. pp. 1522-1528.
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abstract = "Background: Glycoproteins 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. Objective: The modulatory effect of Lex or its glycoconjugates on IgE/TH2 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 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. Conclusion: These 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 implications: The 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.",
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AU - Kawasaki, Hirokazu

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AU - Lee, Reiko T.

AU - Lee, Yuan C.

AU - Huang, Shau Ku

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