The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1998/5/1647-b/ $5.00
The Journal of Experimental Medicine, Volume 187, Number 10, May 18, 1998 1647-1657


Articles

Protective Immunity Does Not Correlate with the Hierarchy of Virus-specific Cytotoxic T Cell Responses to Naturally Processed Peptides

Awen Gallimore*, Tilman Dumrese{ddagger}, Hans Hengartner*, Rolf M. Zinkernagel*, and Hans-Georg Rammensee{ddagger}

From the * Institute of Experimental Immunology, CH-8091 Zürich, Switzerland; and the {ddagger} University of Tübingen, Institute for Cell Biology, 72076 Tübingen, Germany

Infection of C57BL/6 mice with lymphocytic choriomeningitis virus (LCMV) stimulates major histocompatibility complex class I–restricted cytotoxic T cells (CTLs), which normally resolve the infection. Three peptide epitopes derived from LCMV have been shown to bind the mouse class I molecule H-2 Db and to stimulate CTL responses in LCMV-infected mice. This report describes the identity and abundance of each CTL epitope after their elution from LCMV-infected cells. Based on this information, peptide abundance was found to correlate with the magnitude of each CTL response generated after infection with LCMV. Subsequent experiments, performed to determine the antiviral capacity of each CTL specificity, indicate that the quantitative hierarchy of CTL activity does not correlate with the ability to protect against LCMV infection. This report, therefore, indicates that immunodominant epitopes should be defined, not only by the strength of the CTL response that they stimulate, but also by the ability of the CTLs to protect against infection.

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Address correspondence to Awen Gallimore, Molecular Immunology, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, UK. Phone: 44-1865-222413; Fax: 44-1865-222502; E-mail: awen.gallimore{at}ndm.ox.ac.uk

The authors would like to acknowledge Alana Althage, Stefan Stevanovic, Kevin Maloy, Peter Aichele, and Karin Brduscha-Reim for helpful assistance and discussion.

Awen Gallimore is supported by The Wellcome Trust Foundation, Great Britain. This work was also supported by grants from the Deutsch Forschungsgemeinschaft (Leibnizprogramm Ra 369/4-1), the Bundesminister für Bildung, wissenschaft, Forschung und Technologie, the European Union (Biotech2), and the Swiss National Science Foundation (grants 31-32179.91, 31-50884.97, 31-32195.91, and 31-50900.97).

Abbreviations used: ER, endoplasmic reticulum; GP, glycoprotein; L, ligand; LCMV, lymphocytic choriomeningitis virus; NP, nucleoprotein.


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