Immunological tolerance to LCMV antigens differently affects control of acute and chronic virus infection in mice

Eur J Immunol. 2018 Jan;48(1):120-127. doi: 10.1002/eji.201747156. Epub 2017 Sep 15.

Abstract

Cytotoxic T lymphocytes (CTLs) play a key role in the control of lymphocytic choriomeningitis virus (LCMV) infection. In C57BL/6 mice (H-2b ), the CTL response is mainly directed against epitopes from the LCMV glycoprotein (GP) and the nucleoprotein (NP) which represent the two major viral proteins. The role of GP- versus NP-derived epitopes for viral clearance was examined using transgenic (tg) mice ubiquitously expressing LCMV GP and NP, respectively. These mice lack GP- or NP-specific CTLs and show decreased levels of GP- or NP-specific antibodies as a result of tolerance induction. During acute LCMV infection, CTLs specific for GP- and NP-derived epitopes are generated with similar frequencies. Nonetheless, we found that lack of GP- but not of NP-specific CTLs abolished control of acute LCMV infection. In contrast, after high-dose or chronic LCMV infection, virus elimination was delayed to a similar extent in GP- and NP-tg mice. Thus, immunological tolerance to LCMV antigens differently affects virus clearance in acute and chronic infection settings. In addition, our data reveal that immunodominance of H-2b -restricted LCMV-specific CTL epitopes and their antiviral activity do not strictly correlate.

Keywords: Epitopes; Immunodominance; LCMV; T cells; Tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Antibodies, Viral / immunology
  • Antigens, Viral / immunology*
  • Chronic Disease
  • Epitopes, T-Lymphocyte
  • Glycoproteins / immunology*
  • Lymphocytic Choriomeningitis / immunology
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nucleoproteins / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Viral Proteins / immunology

Substances

  • Antibodies, Viral
  • Antigens, Viral
  • Epitopes, T-Lymphocyte
  • Glycoproteins
  • Nucleoproteins
  • Viral Proteins