Oligosaccharide-mediated targeting of dendritic cells and the development of carbohydrate microarrays

Bone-marrowed derived dendritic cells (DCs) constitute a critical arm of the immune system capable of polarizing the immune response toward active immunity or tolerance. Successful therapeutic modulation of DC function in vivo should create opportunities for more potent, efficacious vaccines and, in setting of autoimmunity, strategies aimed at the limiting the numbers and character of autoreactive T cells. This thesis describes work aimed at accessing DCs in vivo by way of cell-surface carbohydrate binding proteins expressed by these cells. Synthetic oligosaccharides bearing a tri(ethylene glycol) linker with a reactive thiol handle were chemically coupled to model antigens to generate oligosaccharide-antigen conjugates. These conjugates were evaluated for their ability to specifically target DCs in vitro. Those oligosaccharide moieties that led to enhanced presentation of model antigen to antigen-specific T cells were evaluated for their ability to access DCs in vivo upon subcutaneous immunization and the immunological outcome of DC targeting was studied in detail. The development of carbohydrate microarrays as tools for the identification of the carbohydrate specificities of carbohydrate-binding proteins (lectins and antibodies) is also described here. High density carbohydrate arrays were generated with synthetic saccharides bearing the aforementioned thiol linker.

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Adams, Eddie William, 1972-

Advisor dc:contributor.advisor

• Peter H. Seeberger.

• Chemistry.

Statement dc:rights

• MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/106721

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/106721