A lymphocytic choriomeningitis virus glycoprotein variant that is retained in the endoplasmic reticulum efficiently cross-primes CD8+ T cell responses

Stefan Freigang, Bruno Eschli, Nicola Harris, Markus Geuking, Katharina Quirin, Sabrina Schrempf, Raphael Zellweger, Jacqueline Weber, Hans Hengartner, Rolf M. Zinkernagel

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22 Citations (Scopus)

Abstract

Recent studies indicate that T cell cross-priming preferentially occurs against long-lived, stable proteins. We have studied cross-priming by using the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV), a protein that normally is not MHC class I cross-presented. This study shows that a C-terminally truncated, noncleavable variant of LCMV-GP led to the accumulation of stable, soluble GP trimers in the endoplasmic reticulum (ER) of the antigen donor cell, and thereby converted LCMV-GP into a potent immunogen for cytotoxic T lymphocyte cross-priming. Immunization of mice with tumor cells expressing an ER-retained LCMV-GP variant cross-primed protective antiviral cytotoxic T lymphocyte responses in vivo at least 10,000-fold better than immunization with cells expressing the cross-presentation-"resistant" wild-type LCMV-GP. Thus the ER is a cellular compartment that can provide antigen for cross-presentation, and modifications affecting stability and subcellular localization of the antigen significantly increase its availability for MHC class I cross-presentation. These findings impinge on vaccine strategies.

Original languageEnglish
Pages (from-to)13426-13431
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number33
DOIs
Publication statusPublished - 14 Aug 2007
Externally publishedYes

Keywords

  • Antigen presentation
  • Cross-presentation
  • Cytotoxic T lymphocytes
  • Vaccination

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