TY - JOUR
T1 - Peptides identified through phage display direct immunogenic antigen to dendritic cells
AU - Curiel, Tyler J.
AU - Morris, Cindy
AU - Brumlik, Michael
AU - Landry, Samuel J.
AU - Finstad, Kristiaan
AU - Nelson, Anne
AU - Joshi, Virendra
AU - Hawkins, Christopher
AU - Alarez, Xavier
AU - Lackner, Andrew
AU - Mohamadzadeh, Mansour
PY - 2004/6/15
Y1 - 2004/6/15
N2 - 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 immunogenity. 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.
AB - 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 immunogenity. 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.
UR - http://www.scopus.com/inward/record.url?scp=2942565923&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=2942565923&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.172.12.7425
DO - 10.4049/jimmunol.172.12.7425
M3 - Article
C2 - 15187120
AN - SCOPUS:2942565923
SN - 0022-1767
VL - 172
SP - 7425
EP - 7431
JO - Journal of Immunology
JF - Journal of Immunology
IS - 12
ER -