| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892;
La Jolla Institute for Allergy and Immunology, and
Epimmune, Inc., San Diego, CA 92121
CD4+ T cells play an important role in hepatitis B virus (HBV) infection by secretion of Th1 cytokines that down-regulate HBV replication, and by promoting CD8+ T cell and B cell responses. We have identified and characterized 10 CD4+ T cell epitopes within polymerase and used them to analyze the immunological effects of long-term antiviral therapy as compared with spontaneous recovery from HBV infection. Candidate epitopes were tested for binding to 14 HLA-DR molecules and in IFN-
ELISPOT and cytotoxicity assays using peripheral blood lymphocytes from 66 HBV-infected patients and 16 uninfected controls. All 10 epitopes bound with high affinity to the most prevalent HLA-DR Ags, were conserved among HBV genomes, and induced IFN- responses from HBV-specific CD4+ T cells. Several epitopes contained nested MHC class I motifs and stimulated HBV-specific IFN- production and cytotoxicity of CD8+ T cells. HBV polymerase-specific responses were more frequent during acute, self-limited hepatitis and after recovery (12 of 18; 67%) than during chronic hepatitis (16 of 48 (33%); p = 0.02). Antiviral therapy of chronic patients restored HBV polymerase and core-specific T cell responses during the first year of treatment, but thereafter, responses decreased and, after 3 years, were no more frequent than in untreated patients. Decreased T cell responsiveness during prolonged therapy was associated with increased prevalence of lamivudine-resistant HBV mutants and increased HBV titers. The data provide a rationale for the combination of antiviral and immunostimulatory therapy. These newly described HBV polymerase epitopes could be a valuable component of a therapeutic vaccine for a large and ethnically diverse patient population.
This article has been cited by other articles:
|
|
 |
|
  A. Joshi, J. Tang, M. Kuzma, J. Wagner, B. Mookerjee, J. Filicko, M. Carabasi, N. Flomenberg, and P. Flomenberg Adenovirus DNA polymerase is recognized by human CD8+ T cells J. Gen. Virol., January 1, 2009; 90(1): 84 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Depla, A. Van der Aa, B. D. Livingston, C. Crimi, K. Allosery, V. De Brabandere, J. Krakover, S. Murthy, M. Huang, S. Power, et al. Rational Design of a Multiepitope Vaccine Encoding T-Lymphocyte Epitopes for Treatment of Chronic Hepatitis B Virus Infections J. Virol., January 1, 2008; 82(1): 435 - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Boni, P. Fisicaro, C. Valdatta, B. Amadei, P. Di Vincenzo, T. Giuberti, D. Laccabue, A. Zerbini, A. Cavalli, G. Missale, et al. Characterization of Hepatitis B Virus (HBV)-Specific T-Cell Dysfunction in Chronic HBV Infection J. Virol., April 15, 2007; 81(8): 4215 - 4225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Gares, K. P. Fischer, S. E. Congly, S. Lacoste, W. R. Addison, D. L. Tyrrell, and K. S. Gutfreund Immunotargeting with CD154 (CD40 Ligand) Enhances DNA Vaccine Responses in Ducks. Clin. Vaccine Immunol., August 1, 2006; 13(8): 958 - 965. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Cuestas, V. L. Mathet, V. Ruiz, M. L. Minassian, C. Rivero, A. Sala, D. Corach, A. Alessio, M. Pozzati, B. Frider, et al. Unusual Naturally Occurring Humoral and Cellular Mutated Epitopes of Hepatitis B Virus in a Chronically Infected Argentine Patient with Anti-HBs Antibodies. J. Clin. Microbiol., June 1, 2006; 44(6): 2191 - 2198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bertoletti and A. J. Gehring The immune response during hepatitis B virus infection J. Gen. Virol., June 1, 2006; 87(6): 1439 - 1449. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
