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 language | English (US) |
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Pages (from-to) | 11047-11051 |
Number of pages | 5 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 88 |
Issue number | 24 |
DOIs | |
State | Published - 1991 |
Externally published | Yes |
Keywords
- T-cell epitope
- Virus mutants
- Virus selection
ASJC Scopus subject areas
- General