Peptides identified through phage display direct immunogenic antigen to dendritic cells.
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.
Curiel
Tyler J
TJ
Department of Medicine, Tulane University Health Science Center, New Orleans, LA 70112, USA.
Morris
Cindy
C
Brumlik
Michael
M
Landry
Samuel J
SJ
Finstad
Kristiaan
K
Nelson
Anne
A
Joshi
Virendra
V
Hawkins
Christopher
C
Alarez
Xavier
X
Lackner
Andrew
A
Mohamadzadeh
Mansour
M
D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D019151:Peptide Library; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D011993:Recombinant Fusion Proteins; D017361:Viral Nonstructural Proteins / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D000956:Antigens, Viral; D016207:Cytokines; D019151:Peptide Library; D010455:Peptides; D011993:Recombinant Fusion Proteins; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases