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Peptides Identified through Phage Display Direct Immunogenic Antigen to Dendritic Cells¹

Tyler J. Curiel^*, Cindy Morris, Michael Brumlik^*, Samuel J. Landry, Kristiaan Finstad^*, Anne Nelson, Virendra Joshi^*, Christopher Hawkins, Xavier Alarez, Andrew Lackner and Mansour Mohamadzadeh^2,*

Departments of ^* Medicine, Microbiology, and Biochemistry, Tulane University Health Science Center, and Tulane National Primate Research Center, New Orleans, LA 70112

Dendritic cells (DC) play a critical role in adaptive immunity by presenting Ag, thereby priming naive T cells. Specific DC-binding peptides were identified using a phage display peptide library. DC-peptides were fused to hepatitis C virus nonstructural protein 3 (NS3) while preserving DC targeting selectivity and Ag immunogenicity. The NS3-DC-peptide fusion protein was efficiently presented to CD4⁺ and CD8⁺ T cells derived from hepatitis C virus-positive blood cells, inducing their activation and proliferation. This immunogenic fusion protein was significantly more potent than NS3 control fusion protein or NS3 alone. In chimeric NOD-SCID mice transplanted with human cells, DC-targeted NS3 primed naive CD4⁺ and CD8⁺ T cells for potent NS3-specific proliferation and cytokine secretion. The capacity of peptides to specifically target immunogenic Ags to DC may establish a novel strategy for vaccine development.

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