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* Jaffe Food Allergy Institute, Department of Pediatrics, Division of Allergy and Immunology, Mount Sinai School of Medicine, New York, NY 10029; and
Department of Pediatrics, Division of Allergy/Immunology, Duke University, Durham, NC 27706
Nonmammalian glycan structures from helminths act as Th2 adjuvants. Some of these structures are also common on plant glycoproteins. We hypothesized that glycan structures present on peanut glycoallergens act as Th2 adjuvants. Peanut Ag (PNAg), but not deglycosylated PNAg, activated monocyte-derived dendritic cells (MDDCs) as measured by MHC/costimulatory molecule up-regulation, and by their ability to drive T cell proliferation. Furthermore, PNAg-activated MDDCs induced 2- to 3-fold more IL-4- and IL-13-secreting Th2 cells than immature or TNF/IL-1-activated MDDCs when cultured with naive CD4+ T cells. Human MDDCs rapidly internalized Ag in a calcium- and glycan-dependent manner consistent with recognition by C-type lectin. Dendritic cell (DC)-specific ICAM-grabbing nonintegrin (DC-SIGN) (CD209) was shown to recognize PNAg by enhanced uptake in transfected cell lines. To identify the DC-SIGN ligand from unfractionated PNAg, we expressed the extracellular portion of DC-SIGN as an Fc-fusion protein and used it to immunoprecipitate PNAg. A single glycoprotein was pulled down in a calcium-dependent manner, and its identity as Ara h 1 was proven by immunolabeling and mass spectrometry. Purified Ara h 1 was found to be sufficient for the induction of MDDCs that prime Th2-skewed T cell responses. Both PNAg and purified Ara h 1 induced Erk 1/2 phosphorylation of MDDCs, consistent with previous reports on the effect of Th2 adjuvants on DCs.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 W.G.S. was supported by National Institutes of Health Grant K12HD052890 and the Food Allergy Initiative.
2 Address correspondence and reprint requests to Dr. Wayne G. Shreffler, Department of Pediatrics, Box 1198, Division of Allergy and Immunology, Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029. E-mail address: wayne.shreffler{at}mssm.edu
3 Abbreviations used in this paper: PAMP, pathogen-associated molecular pattern; dAra h 1, deglycosylated Ara h 1; MDDC, monocyte-derived dendritic cell; DC, dendritic cell; DC-SIGN, DC-specific ICAM-grabbing nonintegrin; dPNAg, deglycosylated peanut Ag; MFI, mean fluorescence intensity; PNAg, peanut Ag; SEA, schistosome egg glycoprotein; SEB, Staphylococcus aureus enterotoxin B.
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