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CD4+ T-cell–epitope escape mutant virus selected in vivo

Nature Medicine volume 7, pages 795–800 (2001)Cite this article

Abstract

Mutations in viral genomes that affect T-cell–receptor recognition by CD8+ cytotoxic T lymphocytes have been shown to allow viral evasion from immune surveillance during persistent viral infections. Although CD4+ T-helper cells are crucially involved in the maintenance of effective cytotoxic T-lymphocyte and neutralizing-antibody responses, their role in viral clearance and therefore in imposing similar selective pressures on the virus is unclear. We show here that transgenic virus-specific CD4+ Tcells, transferred into mice persistently infected with lymphocytic choriomeningitis virus, select for T-helper epitope mutant viruses that are not recognized. Together with the observed antigenic variation of the same T-helper epitope during polyclonal CD4+ T-cell responses in infected pore-forming protein-deficient C57BL/6 mice, this finding indicates that viral escape from CD4+ T lymphocytes is a possible mechanism of virus persistence.

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Figure 1: LCMV control in Pfp−/− mice.
Figure 2: Altered recognition of mutated T-helper epitopes by the transgenic TCR.
Figure 3: CD4+ T-cell antagonism by naturally occurring T-helper epitope variants.
Figure 4: Effect of LCMV T-helper epitope escape in vivo.
Figure 5: LCMV-specific MHC class II-restricted cytotoxicity in vitro.

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Acknowledgements

We appreciate the help in the generation of DNA sequence data of D. Zimmermann and his group. This work was supported by the Swiss National Science Foundation grants 31.50900.97 and 31.50884.97, and the Kanton of Zurich.

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Author notes

  1. Adrian Ciurea and Lukas Hunziker: A.C. and L.H. contributed equally to this study.

Authors and Affiliations

  1. Institute for Experimental Immunology, University Hospital, Zurich, Switzerland

    Adrian Ciurea, Lukas Hunziker, Marianne M. A. Martinic, Annette Oxenius, Hans Hengartner & Rolf M. Zinkernagel

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  1. Adrian Ciurea
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Correspondence to Adrian Ciurea.

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Ciurea, A., Hunziker, L., Martinic, M. et al. CD4+ T-cell–epitope escape mutant virus selected in vivo. Nat Med 7, 795–800 (2001). https://doi.org/10.1038/89915

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