title: Priming of CD8+ T cells against cytomegalovirus-encoded antigens is dominated by cross-presentation.
abstract: CMV can infect dendritic cells (DCs), and direct Ag presentation could, therefore, lead to the priming of CMV-specific CD8(+) T cells. However, CMV-encoded immune evasins severely impair Ag presentation in the MHC class I pathway; thus, it is widely assumed that cross-presentation drives the priming of antiviral T cells. We assessed the contribution of direct versus cross priming in mouse CMV (MCMV) infection using recombinant viruses. DCs infected with an MCMV strain encoding the gB498 epitope from HSV-1 were unable to stimulate in vitro naive gB498-specific CD8(+) T cells from TCR transgenic mice. Infection of C57BL/6 mice with this recombinant virus led, however, to the generation of abundant numbers of gB498-specific T cells in vivo. Of the DC subsets isolated from infected mice, only CD8α(+) DCs were able to stimulate naive T cells, suggesting that this DC subset cross-presents MCMV-encoded Ag in vivo. Upon infection of mice with MCMV mutants encoding Ag that can either be well or hardly cross-presented, mainly CD8(+) T cells specific for cross-presented epitopes were generated. Moreover, even in the absence of immune evasion genes interfering with MHC class I-mediated Ag presentation, priming of T cells to Ag that can only be presented directly was not observed. We conclude that the host uses mainly DCs capable of cross-presentation to induce the CMV-specific CD8(+) T cell response during primary, acute infection and discuss the implications for the development of a CMV vaccine.
authors: Department of Virology, Hannover Medical School, 30625 Hannover, Germany.
authors: Andreas
authors: A
authors: Busche
authors: Adan Chari
authors: AC
authors: Jirmo
authors: Suzanne P M
authors: SP
authors: Welten
authors: Jasmin
authors: J
authors: Zischke
authors: Julia
authors: J
authors: Noack
authors: Hannelore
authors: H
authors: Constabel
authors: Anna-Katherina
authors: AK
authors: Gatzke
authors: Kirsten A
authors: KA
authors: Keyser
authors: Ramon
authors: R
authors: Arens
authors: Georg M N
authors: GM
authors: Behrens
authors: Martin
authors: M
authors: Messerle
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000821:virology; D000956:Antigens, Viral / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D002999:Clone Cells; D045142:Cross-Priming / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006566:Herpesviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018146:Muromegalovirus / Q000235:genetics / Q000276:immunology*
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte