MHC class I and non-MHC-linked capacity for generating an anti-viral CTL response determines susceptibility to CTL exhaustion and establishment of virus persistence in mice

D. Moskophidis, F. Lechner, H. Hengartner, R. M. Zinkernagel

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

The influence of the murine MHC gene complex H-2 class I alleles or of the genetic background and the role of virus variants on establishment of a persistent infection with lymphocytic choriomeningitis virus (LCMV) was analyzed in immunocompetent mice of H-2(d) haplotype by evaluation of cytotoxic T cell responses. Susceptibility to establishment of a virus carrier state increased in various H-2(d) mice with lower CTL response and slower CTL kinetics. Low responder BALB/c-H-2(dm2), lacking H-2L(d) molecules to present the major T cell epitope amino acids 118-126 of the LCMV nucleoprotein or DBA/2 mice possessing relatively few CD8+ T cells, were more susceptible than high responder BALB/c mice expressing H-2L(d). Additional critical factors were LCMV isolate and dose of infection. The rapidly replicating LCMV-DOCILE and CI 13 Armstrong induced viral persistence readily, whereas the slowly replicating parental virus strains WE or Armstrong did not. The presented findings illustrate a model of MHC-linked or MHC-unlinked susceptibility for virus persistence and may help to explain pathogeneses of chronic virus infections in humans that are often associated with slowly progressing immunopathology.

Original languageEnglish (US)
Pages (from-to)4976-4983
Number of pages8
JournalJournal of Immunology
Volume152
Issue number10
StatePublished - Jan 1 1994
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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