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

doi:10.1084/jem.187.10.1647

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J. Exp. Med., Volume 187, Number 10, May 18, 1998 1647-1657

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

By Awen Gallimore,^* Tilman Dumrese, Hans Hengartner,^* Rolf M. Zinkernagel,^* and Hans-Georg Rammensee

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

Infection of C57BL/6 mice with lymphocytic choriomeningitis virus (LCMV) stimulates major histocompatibility complex classI-restricted cytotoxic T cells (CTLs), which normally resolvethe infection. Three peptide epitopes derived from LCMV have beenshown to bind the mouse class I molecule H-2 D^b and to stimulate CTL responses in LCMV-infected mice. This reportdescribes the identity and abundance of each CTL epitope aftertheir elution from LCMV-infected cells. Based on this information,peptide abundance was found to correlate with the magnitude ofeach CTL response generated after infection with LCMV. Subsequentexperiments, performed to determine the antiviral capacity ofeach CTL specificity, indicate that the quantitative hierarchyof CTL activity does not correlate with the ability to protectagainst LCMV infection. This report, therefore, indicates thatimmunodominant epitopes should be defined, not only by the strengthof the CTL response that they stimulate, but also by the abilityof the CTLs to protect against infection.

Key words: cytotoxic T cell; lymphocytic choriomeningitis virus; antiviral protection; peptide elution; adoptive transfer

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