Priming of CD8+ T cells against cytomegalovirus-encoded antigens is dominated by cross-presentation

A Busche, AC Jirmo, SPM Welten, J Zischke… - The Journal of …, 2013 - journals.aai.org
A Busche, AC Jirmo, SPM Welten, J Zischke, J Noack, H Constabel, AK Gatzke, KA Keyser…
The Journal of Immunology, 2013journals.aai.org
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 gB 498 epitope from HSV-1 were unable to …
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 gB 498 epitope from HSV-1 were unable to stimulate in vitro naive gB 498-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 gB 498-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.
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