title: Cytomegalovirus misleads its host by priming of CD8 T cells specific for an epitope not presented in infected tissues.
abstract: 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.
authors.affiliation: Institute for Virology, Johannes Gutenberg-University, Hochhaus am Augustusplatz, 55101 Mainz, Germany.
authors.forename: Rafaela
authors.initials: R
authors.lastname: Holtappels
authors.forename: Jürgen
authors.initials: J
authors.lastname: Podlech
authors.forename: Marcus-Folker
authors.initials: MF
authors.lastname: Pahl-Seibert
authors.forename: Markus
authors.initials: M
authors.lastname: Jülch
authors.forename: Doris
authors.initials: D
authors.lastname: Thomas
authors.forename: Christian O
authors.initials: CO
authors.lastname: Simon
authors.forename: Markus
authors.initials: M
authors.lastname: Wagner
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Reddehase
mesh_terms: D019264:Adoptive Transfer; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology* / Q000472:pathogenicity*; D003586:Cytomegalovirus Infections / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D018189:Immunomagnetic Separation; D008213:Lymphocyte Activation