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Carbohydrate‐Mediated Targeting of Antigen to Dendritic Cells Leads to Enhanced Presentation of Antigen to T Cells
Author(s) -
Adams Eddie W.,
Ratner Daniel M.,
Seeberger Peter H.,
Hacohen Nir
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200700310
Subject(s) - antigen , antigen presentation , antigen presenting cell , major histocompatibility complex , antigen processing , chemistry , ovalbumin , biology , immunology , immune system , microbiology and biotechnology , mhc class i , t cell
The unique therapeutic value of dendritic cells (DCs) for the treatment of allergy, autoimmunity and transplant rejection is predicated upon our ability to selectively deliver antigens, drugs or nucleic acids to DCs in vivo. Here we describe a method for delivering whole protein antigens to DCs based on carbohydrate‐mediated targeting of DC‐expressed lectins. A series of synthetic carbohydrates was chemically‐coupled to a model antigen, ovalbumin (OVA), and each conjugate was evaluated for its ability to increase the efficiency of antigen presentation by murine DCs to OVA‐specific T cells (CD4 + and CD8 + ). In vitro data are presented that demonstrate that carbohydrate modification of OVA leads to a 50‐fold enhancement of presentation of antigenic peptide to CD4 + T cells. A tenfold enhancement is observed for CD8 + T cells; this indicates that the targeted lectin(s) can mediate cross‐presentation of antigens on MHC class I. Our data indicate that the observed enhancements in antigen presentation are unique to OVA that is conjugated to complex oligosaccharides, such as a high‐mannose nonasaccharide, but not to monosaccharides. Taken together, our data suggest that a DC targeting strategy that is based upon carbohydrate‐lectin interactions is a promising approach for enhancing antigen presentation via class I and class II molecules.

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