Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Overcoming T cell tolerance to the hepatitis B virus surface antigen in hepatitis B virus-transgenic mice

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Sette, A. D.
  • Oseroff, C.
  • Sidney, J.
  • Alexander, J.
  • Chesnut, R. W.
  • Kakimi, K.
  • Guidotti, Luca
  • Chisari, Francis

publication date

  • January 2001

journal

  • Journal of Immunology  Journal

abstract

  • The sequence of the hepatitis B virus (HBV) major envelope (Env) protein (ayw subtype) was scanned for the presence of H-2(d,b) motifs. Following binding and immunogenicity testing, two new H-2(d)-restricted epitopes (Env.362 and Env.364) were identified. These epitopes induced CTLs capable of recognizing naturally processed HBV-Env, but were apparently generated with lower efficiency than the previously defined dominant Env.28 epitope. Next, HBV-transgenic mice that express all of the HBV proteins and produce fully infectious particles were immunized with a mixture of lipopeptides encompassing the Env.28, Env.362, and Env.364 epitopes. Significant CTL responses were obtained, but they had no effect on viral replication in the liver, nor did they induce an inflammatory liver disease. However, in adoptive transfer experiments, CTL lines generated from the HBV-transgenic mice following immunization were able to inhibit viral replication in vivo without causing hepatitis. This is in contrast to CTL lines derived from nontransgenic mice that displayed both antiviral and cytopathic effects, presumably because they displayed higher avidity for the viral epitopes than the transgenic CTLs. These results suggest that T cell tolerance to HBV can be broken with appropriate immunization but the magnitude and characteristics of the resultant T cell response are significantly different from the response in HBV-naive individuals since their antiviral potential is stronger than their cytotoxic potential. This has obvious implications for immunotherapy of chronic HBV infection.

subject areas

  • Adoptive Transfer
  • Animals
  • Antigen Presentation
  • Cytotoxicity, Immunologic
  • Dose-Response Relationship, Immunologic
  • Down-Regulation
  • Epitopes, T-Lymphocyte
  • Hepatitis B
  • Hepatitis B Surface Antigens
  • Hepatitis B virus
  • Immune Tolerance
  • Immunodominant Epitopes
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Peptide Fragments
  • T-Lymphocytes, Cytotoxic
  • Tumor Cells, Cultured
  • Viral Envelope Proteins
scroll to property group menus

Identity

International Standard Serial Number (ISSN)

  • 0022-1767

PubMed ID

  • 11145724
scroll to property group menus

Additional Document Info

start page

  • 1389

end page

  • 1397

volume

  • 166

issue

  • 2

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support