Antigen coupled with Lewis-x trisaccharides elicits potent immune responses in mice.
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-kappaB, in bone marrow-derived dendritic cells from BALB/c mice, suggesting that Le(x)-induced suppression of IL-12p70 results in an enhanced T(H)2 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.


CONCLUSIONS
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.


CONCLUSIONS
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.
Hsu
Shih-Chang
SC
Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA. skhuang@jhmi.edu
Tsai
Tsung-Hsien
TH
Kawasaki
Hirokazu
H
Chen
Chien-Ho
CH
Plunkett
Beverly
B
Lee
Reiko T
RT
Lee
Yuan C
YC
Huang
Shau-Ku
SK
D000276:Adjuvants, Immunologic / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002417:Cattle; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007983:Lewis Blood Group Antigens / Q000276:immunology* / Q000378:metabolism; D016256:Lewis X Antigen / Q000031:analogs & derivatives; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D012710:Serum Albumin, Bovine / Q000276:immunology* / Q000378:metabolism; D014312:Trisaccharides / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D008070:Lipopolysaccharides; D014312:Trisaccharides; C110530:galactosyl-(1,4)-fucopyranosyl-(1,3)-N-acetylglucosamine; D018664:Interleukin-12; D012710:Serum Albumin, Bovine