The Journal of Experimental Medicine
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Published online 29 December 2003 doi:10.1084/jem.20031582
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 1, 131-136
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Brief Definitive Report

 Cytomegalovirus Misleads Its Host by Priming of CD8 T Cells Specific for an Epitope Not Presented in Infected Tissues

Rafaela Holtappels1, Jürgen Podlech1, Marcus-Folker Pahl-Seibert1, Markus Jülch2, Doris Thomas1, Christian O. Simon1, Markus Wagner3 and Matthias J. Reddehase1

1 Institute for Virology, Johannes Gutenberg-University, 55101 Mainz, Germany
2 Tumor Vaccination Centre, Johannes Gutenberg-University, 55101 Mainz, Germany
3 Max von Pettenkofer Institute, Department for Virology, Gene Center of the Ludwig Maximilians-University, 81377 Munich, Germany

Address correspondence to Matthias J. Reddehase, Institute for Virology, Johannes Gutenberg-University, Hochhaus am Augustusplatz, 55101 Mainz, Germany. Phone: 49-6131-3933650; Fax: 49-6131-3935604; email: Matthias.Reddehase{at}uni-mainz.de

Cytomegaloviruses (CMVs) code for several proteins that inhibit the presentation of antigenic peptides to CD8 T cells. Although the molecular mechanisms of CMV interference with the major histocompatibility complex class I pathway are long understood, surprisingly little evidence exists to support a role in vivo. Here we document the first example of the presentation of an antigenic peptide being blocked by a CMV immune evasion protein in organs relevant to CMV disease. Although this Db-restricted peptide, which is derived from the antiapoptotic protein M45 of murine CMV (mCMV), is classified as an immunodominant peptide based on response magnitude and long-term memory, adoptive transfer of M45 epitope-specific CD8 T cells did not protect against infection with wild-type mCMV. Notably, the same cells protected C57BL/6 mice infected with an mCMV mutant in which immune evasion protein m152/gp40 is deleted. These data indicate that direct presentation or cross-presentation of an antigenic peptide by professional antigen-presenting cells can efficiently prime CD8 T cells that fail in protection against CMV organ disease because m152/gp40 prevents presentation of this peptide in pathogenetically relevant tissue cells.

Key Words: immunodominance • immune evasion • immune control • antigen presentation • cross-priming

M. Wagner's present address is Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115.


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