Publication year
2012Number of pages
10 p.
Source
European Journal of Immunology, 42, 8, (2012), pp. 1989-1998ISSN
Annotation
01 augustus 2012
Publication type
Article / Letter to editor
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Organization
Tumorimmunology
Rheumatology
Journal title
European Journal of Immunology
Volume
vol. 42
Issue
iss. 8
Languages used
English (eng)
Page start
p. 1989
Page end
p. 1998
Subject
NCMLS 1: Infection and autoimmunity N4i 4: Auto-immunity, transplantation and immunotherapy; NCMLS 3: Tissue engineering and pathology; ONCOL 3: Translational research NCMLS 2: Immune RegulationAbstract
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.
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- Faculty of Medical Sciences [90373]
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