Immunobiology of cytotoxic T-cell resistant virus variants

Studies on lymphocytic choriomeningitis virus (LCMV)

Dimitrios Moskofidis, Rolf M. Zinkernagel

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

Replication of the genetically variable lymphocytic choriomeningitis virus (LCMV) gives rise to a pool of variant viruses. Under the selection pressure exerted by a strong but narrow repertoire of antiviral cytotoxic T-cells (CTL) i.e. monoclonal or polyclonal monoepitope, variant viruses emerge that contain point mutations in the nucleotide sequence encoding antigenic CTL epitopes; these variants cart be selected in both infected mice and cell cultures. These mutations permit infected cells to escape CTL recognition by altering the ability of the mutant peptides to bind MHC class-I-molecules or by interfering with the ability of T-cell receptors to interact with the mutant peptide/MHC complex. Because viral infections often trigger a polyclonal repertoire of antiviral CTL to multiple epitopes, the likelihood of selection of CTL resistant variants is probably low, but not impossible. Our empirical observations suggest that antigenic variations, even if they only occur in a part of the available CTL epitope, may exert significant effects on the subtle biological equilibrium established between virus and host immune system. This can reduce immunological control of the pathogen population, and so permit persistence of viral infection and promote disease progression.

Original languageEnglish (US)
Pages (from-to)3-11
Number of pages9
JournalSeminars in Virology
Volume7
Issue number1
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Fingerprint

Lymphocytic choriomeningitis virus
Viruses
T-Lymphocytes
T-Lymphocyte Epitopes
Virus Diseases
Antiviral Agents
Antigenic Variation
Peptides
T-Cell Antigen Receptor
Point Mutation
Disease Progression
Epitopes
Immune System
Cell Culture Techniques
Pressure
Mutation
Population

Keywords

  • CTL escape variant virus
  • Immunobiology
  • Immunodominance
  • LCMV
  • Viral persistence

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Immunobiology of cytotoxic T-cell resistant virus variants : Studies on lymphocytic choriomeningitis virus (LCMV). / Moskofidis, Dimitrios; Zinkernagel, Rolf M.

In: Seminars in Virology, Vol. 7, No. 1, 01.01.1996, p. 3-11.

Research output: Contribution to journalReview article

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