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Eur J Immunol. 2012 Aug;42(8):1989-98. doi: 10.1002/eji.201142258.

Antibodies and carbohydrate ligands binding to DC-SIGN differentially modulate receptor trafficking.

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1
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Abstract

DCs are regarded as key APCs that initiate humoral and cellular immune responses. Consequently, targeted delivery of Ag toward DC-specific receptors enhances vaccine efficacy. DC-SIGN is a C-type lectin receptor that facilitates DC-specific delivery of Ag. This is accomplished by conjugating Ag to receptor-specific Ab or carbohydrate ligands that bind to its carbohydrate recognition domain. Here, we investigated the fate of DC-SIGN following receptor triggering with Ab. Both whole and single-chain Ab induced rapid internalization of about half of the surface receptor molecules. Biochemical studies showed that about half of the receptor molecules were still intracellular after 3 h, while minimal or no resurfacing of internalized or newly synthesized unbound DC-SIGN molecules was observed. Prolonged exposure of DCs to DC-SIGN Ab, but not carbohydrate ligands, resulted in reduced receptor expression levels, which lasted up to 2 days following removal of the Ab. In addition, exposure to DC-SIGN Ab reduced the ability of the receptor to internalize. Consequently, DC-SIGN showed a poor ability to accumulate targeting Abs within DCs. Vaccine efficacy may therefore be enhanced by strategies increasing the amount of Ag entering via a single receptor molecule, such as the use of targeting moieties allowing DC-SIGN recycling or Ab-coated vaccine carriers.

PMID:
22653683
DOI:
10.1002/eji.201142258
[Indexed for MEDLINE]
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