Hyaluronic Acid Graft Polymers Displaying Peptide Antigen Modulate Dendritic Cell Response in Vitro

A novel oxime grafting scheme was utilized to conjugate an ICAM-1 ligand (LABL), a cellular antigen ovalbumin (OVA), or both peptides simultaneously to hyaluronic acid (HA). Samples of HA only and the various peptide grafted HA were found to bind to dendritic cells (DCs). HA with grafted LABL and OV...

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Bibliographic Details
Published in:Molecular pharmaceutics 2014-01, Vol.11 (1), p.367-373
Main Authors: Chittasupho, Chuda, Sestak, Joshua, Shannon, Laura, Siahaan, Teruna J, Vines, Charlotte M, Berkland, Cory
Format: Article
Language:English
Subjects:
Animals
Antigen-Presenting Cells - immunology
Antigen-Presenting Cells - metabolism
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Cells, Cultured
Cytokines - metabolism
Dendritic Cells - immunology
Dendritic Cells - metabolism
Enzyme-Linked Immunosorbent Assay
Hyaluronic Acid - metabolism
In Vitro Techniques
Intercellular Adhesion Molecule-1 - chemistry
Intercellular Adhesion Molecule-1 - metabolism
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Ovalbumin - metabolism
Peptide Fragments - metabolism
Polymers - chemistry
Polymers - metabolism
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
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Summary:A novel oxime grafting scheme was utilized to conjugate an ICAM-1 ligand (LABL), a cellular antigen ovalbumin (OVA), or both peptides simultaneously to hyaluronic acid (HA). Samples of HA only and the various peptide grafted HA were found to bind to dendritic cells (DCs). HA with grafted LABL and OVA showed the greatest binding to DCs. Dendritic cells treated with HA, HA with grafted LABL, or HA with grafted LABL and OVA significantly suppressed T cell and DC conjugate formation and T cell proliferation and reduced proinflammatory cytokine production compared to untreated cells. These results suggest that HA serves as an effective backbone for multivalent ligand presentation for inhibiting T cell response to antigen presentation. In addition, multivalent display of both antigen and an ICAM-1 inhibitor (LABL) may enhance binding to DCs and could potentially disrupt cellular signaling leading to autoimmunity.
ISSN:1543-8384
1543-8392
DOI:10.1021/mp4003909