In vitro selection of lymphocytic choriomeningitis virus escape mutants by cytotoxic T lymphocytes

Toni Aebischer, Demetrius Moskophidis, Urs Hoffmann Rohrer, Rolf M. Zinkernagel, Hans Hengartner

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

Cytotoxic T lymphocyte (CTL)-mediated cytolysis is induced via the interaction of the specific T-cell antigen receptor and the peptidic viral antigen associated with the major histocompatibility complex class I antigen. Here we demonstrate in vitro that lymphocytic choriomeningitis virus (LCMV) can escape the cytotoxic activity of LCMV-specific cloned CTLs by single amino acid changes within the recognized T-cell epitope defined by residues 275-289 of the LCMV glycoprotein [LCMV-GP-(275-289)]. LCMV-infected fibroblasts at a multiplicity of infection of 10-3 exposed to virus-specific CTL at an effector-to-target cell ratio of 4:14 hr after infection was optimal for virus mutant selection. The selections were carried out with three LCMV-GP-(275-289)-specific CTL clones expressing T-cell antigen receptors containing the identical variable gene segments Vα4 and Vβ10 but different junctional regions; selection was also possible with LCMV-GP(275-289)-specific cytotoxic polyclonal T cells. The most common escape mutation was an amino acid change of asparagine (AAT) to aspartic acid (GAT) at position 280; an additional mutation was glycine (GGT) to aspartic acid (GAT) at position 282. The results presented show that relevant point mutations within the T-cell epitope of LCMV-GP-(275-289) occur frequently and that they are selectable in vitro by CTLs.

Original languageEnglish (US)
Pages (from-to)11047-11051
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number24
DOIs
StatePublished - Jan 1 1991
Externally publishedYes

Keywords

  • T-cell epitope
  • Virus mutants
  • Virus selection

ASJC Scopus subject areas

  • General

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