The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Riedl, P.
Right arrow Articles by Schirmbeck, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Riedl, P.
Right arrow Articles by Schirmbeck, R.
The Journal of Immunology, 2002, 168: 4951-4959.
Copyright © 2002 by The American Association of Immunologists

Priming Th1 Immunity to Viral Core Particles Is Facilitated by Trace Amounts of RNA Bound to Its Arginine-Rich Domain1

Petra Riedl*, Detlef Stober*, Claude Oehninger*, Karl Melber{dagger}, Jörg Reimann* and Reinhold Schirmbeck2,*

* Institute of Medical Microbiology and Immunology, University of Ulm, Ulm, Germany; and {dagger} Rhein Biotech, Düsseldorf, Germany

Particulate hepatitis B core Ag (C protein) (HBcAg) and soluble hepatitis B precore Ag (E protein) (HBeAg) of the hepatitis B virus share >70% of their amino acid sequence and most T and B cell-defined epitopes. When injected at low doses into mice, HBcAg particles prime Th1 immunity while HBeAg protein primes Th2 immunity. HBcAg contains 5–20 ng RNA/µg protein while nucleotide binding to HBeAg is not detectable. Deletion of the C-terminal arginine-rich domain of HBcAg generates HBcAg-144 or HBcAg-149 particles (in which >98% of RNA binding is lost) that prime Th2-biased immunity. HBcAg particles, but not truncated HBcAg-144 or -149 particles stimulate IL-12 p70 release by dendritic cells and IFN-{gamma} release by nonimmune spleen cells. The injection of HBeAg protein or HBcAg-149 particles into mice primes Th1 immunity only when high doses of RNA (i.e., 20–100 µg/mouse) are codelivered with the Ag. Particle-incorporated RNA has thus a 1000-fold higher potency as a Th1-inducing adjuvant than free RNA mixed to a protein Ag. Disrupting the particulate structure of HBcAg releases RNA and abolishes its Th1 immunity inducing potency. Using DNA vaccines delivered intradermally with the gene gun, inoculation of 1 µg HBcAg-encoding pCI/C plasmid DNA primes Th1 immunity while inoculation of 1 µg HBeAg-encoding pCI/E plasmid DNA or HBcAg-149-encoding pCI/C-149 plasmid DNA primes Th2 immunity. Expression data show eukaryotic RNA associated with HBcAg, but not HBeAg, expressed by the DNA vaccine. Hence, codelivery of an efficient, intrinsic adjuvant (i.e., nanogram amounts of prokaryotic or eukaryotic RNA bound to arginine-rich sequences) by HBcAg nucleocapsids facilitates priming of anti-viral Th1 immunity.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
B. O. Lee, A. Tucker, L. Frelin, M. Sallberg, J. Jones, C. Peters, J. Hughes, D. Whitacre, B. Darsow, D. L. Peterson, et al.
Interaction of the Hepatitis B Core Antigen and the Innate Immune System
J. Immunol., June 1, 2009; 182(11): 6670 - 6681.
[Abstract] [Full Text] [PDF]

Home page
 CVIHome page
Z. Wang, L. Xiang, J. Shao, and Z. Yuan
The 3' CCACCA Sequence of tRNAAla(UGC) Is the Motif That Is Important in Inducing Th1-Like Immune Response, and This Motif Can Be Recognized by Toll-Like Receptor 3.
Clin. Vaccine Immunol., July 1, 2006; 13(7): 733 - 739.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Cooper, G. Tal, O. Lider, and Y. Shaul
Cytokine Induction by the Hepatitis B Virus Capsid in Macrophages Is Facilitated by Membrane Heparan Sulfate and Involves TLR2
J. Immunol., September 1, 2005; 175(5): 3165 - 3176.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
P. Vanlandschoot, F. Van Houtte, P. Ulrichts, J. Tavernier, and G. Leroux-Roels
Immunostimulatory potential of hepatitis B nucleocapsid preparations: lipopolysaccharide contamination should not be overlooked
J. Gen. Virol., February 1, 2005; 86(2): 323 - 331.
[Abstract] [Full Text] [PDF]

Home page
 J. Gen. Virol.Home page
P. Vanlandschoot, F. Van Houtte, B. Serruys, and G. Leroux-Roels
The arginine-rich carboxy-terminal domain of the hepatitis B virus core protein mediates attachment of nucleocapsids to cell-surface-expressed heparan sulfate
J. Gen. Virol., January 1, 2005; 86(1): 75 - 84.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
F. Heil, H. Hemmi, H. Hochrein, F. Ampenberger, C. Kirschning, S. Akira, G. Lipford, H. Wagner, and S. Bauer
Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8
Science, March 5, 2004; 303(5663): 1526 - 1529.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Storni, C. Ruedl, K. Schwarz, R. A. Schwendener, W. A. Renner, and M. F. Bachmann
Nonmethylated CG Motifs Packaged into Virus-Like Particles Induce Protective Cytotoxic T Cell Responses in the Absence of Systemic Side Effects
J. Immunol., February 1, 2004; 172(3): 1777 - 1785.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. Schirmbeck, P. Riedl, R. Zurbriggen, S. Akira, and J. Reimann
Antigenic Epitopes Fused to Cationic Peptide Bound to Oligonucleotides Facilitate Toll-Like Receptor 9-Dependent, but CD4+ T Cell Help-Independent, Priming of CD8+ T Cells
J. Immunol., November 15, 2003; 171(10): 5198 - 5207.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.