title: Antigen-presenting cells of haematopoietic origin prime cytomegalovirus-specific CD8 T-cells but are not sufficient for driving memory inflation during viral latency.
abstract: Expansion of the CD8 T-cell memory pool, also known as 'memory inflation', for certain but not all viral epitopes in latently infected host tissues is a special feature of the immune response to cytomegalovirus. The L(d)-presented murine cytomegalovirus (mCMV) immediate-early (IE) 1 peptide is the prototype of an epitope that is associated with memory inflation. Based on the detection of IE1 transcripts in latently infected lungs it was previously proposed that episodes of viral gene expression and antigenic activity due to desilencing of a limited number of viral genes may drive epitope-specific memory inflation. This would imply direct antigen presentation through latently infected host tissue cells rather than cell death-associated cross-presentation of viral antigens derived from productively infected cells through uninfected, professional antigen-presenting cells (profAPCs). To address the role of bone marrow-derived profAPCs in CD8 T-cell priming and memory to mCMV, we have used here a combined sex-mismatched and MHC class-I mismatched dual-marker bone marrow chimera model in which presentation of the IE1 epitope is restricted to donor-derived sry(+)L(d+) cells of haematopoietic differentiation lineages. Successful CD8 T-cell priming specific for the L(d)- and D(d)-presented inflationary epitopes IE1 and m164, respectively, but selective failure in IE1 epitope-specific memory inflation in these chimeras indicates different modes of antigen presentation involved in CD8 T-cell priming and memory inflation. These data suggest that memory inflation during mCMV latency requires expression of the epitope-presenting MHC class-I molecule by latently infected non-haematopoietic host tissue cells and thus predicts a role for direct antigen presentation in memory inflation.
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131 Mainz, Germany.
authors.forename: Christof K
authors.initials: CK
authors.lastname: Seckert
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131 Mainz, Germany.
authors.forename: Sina I
authors.initials: SI
authors.lastname: Schader
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131 Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Ebert
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131 Mainz, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Thomas
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131 Mainz, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Freitag
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131 Mainz, Germany.
authors.forename: Angélique
authors.initials: A
authors.lastname: Renzaho
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131 Mainz, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Podlech
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131 Mainz, Germany.
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Reddehase
authors.affiliation: Institute for Virology, University Medical Center of the Johannes Gutenberg-University, Obere Zahlbacher Strasse 67, Hochhaus am Augustusplatz, 55131 Mainz, Germany.
authors.forename: Rafaela
authors.initials: R
authors.lastname: Holtappels
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D017874:Immediate-Early Proteins / Q000276:immunology; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000276:immunology* / Q000502:physiology; D017735:Virus Latency / Q000276:immunology*
chemical_list: D000939:Epitopes; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins