Carbohydrate-mediated targeting of antigen to dendritic cells leads to enhanced presentation of antigen to T cells.
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.
Adams
Eddie W
EW
Center for Immunology and Inflammatory Diseases and Division of Rheumatology, Allergy and Immununology, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th Street, Charlestown, MA 02129, USA.
Ratner
Daniel M
DM
Seeberger
Peter H
PH
Hacohen
Nir
N
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology* / Q000502:physiology; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007167:Immunotherapy; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009844:Oligosaccharides / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D037181:Lectins, C-Type; D009844:Oligosaccharides; D011956:Receptors, Cell Surface; D010047:Ovalbumin