Acquisition of MHC:Peptide Complexes by Dendritic Cells Contributes to the Generation of Antiviral CD8+ T Cell Immunity In Vivo

Abstract

There is an increasing body of evidence suggesting that the transfer of preformed MHC class I:peptide complexes between a virus-infected cell and an uninfected APC, termed cross-dressing, represents an important mechanism of Ag presentation to CD8+ T cells in host defense. However, although it has been shown that memory CD8+ T cells can be activated by uninfected dendritic cells (DCs) cross-dressed by Ag from virus-infected parenchymal cells, it is unknown whether conditions exist during virus infection in which naive CD8+ T cells are primed and differentiate to cytolytic effectors through cross-dressing, and indeed which DC subset would be responsible. In this study, we determine whether the transfer of MHC class I:peptide complexes between infected and uninfected murine DC plays a role in CD8+ T cell priming to viral Ags in vivo. We show that MHC class I:peptide complexes from peptide-pulsed or virus-infected DCs are indeed acquired by splenic CD8α− DCs in vivo. Furthermore, the acquired MHC class I:peptide complexes are functional in that they induced Ag-specific CD8+ T cell effectors with cytolytic function. As CD8α− DCs are poor cross-presenters, this may represent the main mechanism by which CD8α− DCs present exogenously encountered Ag to CD8+ T cells. The sharing of Ag as preformed MHC class I:peptide complexes between infected and uninfected DCs without the restraints of Ag processing may have evolved to accurately amplify the response and also engage multiple DC subsets critical in the generation of strong antiviral immunity.

Langerin negative dendritic cells promote potent CD8 + T-cell priming by skin delivery of live adenovirus vaccine microneedle arrays

“…+ T-cell priming in the absence of Lang + DCs, likely by a direct route of Ag presentation but conceivably also indirectly as cross-dressed Ag, a mechanism of Ag presentation by CD8α − DCs for which there is increasing evidence (23,24).…”

Impaired Direct Priming of CD8 T Cells by Donor-Derived Cytomegalovirus Following Kidney Transplantation

“…These include direct presentation by infected donor antigen-presenting cells (APCs), presentation by recipient APCs "cross-dressed" with donor-derived MHC:viral peptide complexes transferred from donor immune or parenchymal cells, and cross-presentation by recipient APCs that have engulfed and processed circulating virions. 14,15 Recipients' failure to develop CD8+ immune responses through donor-specific HLA alleles suggests that priming and expansion of immune responses to donor-transmitted CMV do not result from direct presentation or cross-dressing. This novel finding with regard to transplantation-associated viral transmission resonates with data from models of murine CMV, suggesting cross-presentation as the primary pathway to antiviral immunity, [16][17][18] with direct priming inhibited due to CMV-mediated downregulation of activating co-stimulatory molecules (such as CD86) and upregulation of inhibitory ligands (such as PD-L1) on APCs, [19][20][21] along with inhibition of dendritic cell maturation and antigen presentation.…”

Mucosal Dendritic Cells

“…Alternatively, some DCs might also acquire preformed MHCI-peptide complexes from other cells, a process called cross-dressing Smyth et al, 2012). DCs that migrated to the lymph node after IAV can be virus infected, but this happens only after infection with higher inocula (Legge and Braciale, 2005) and the CD103 + cDC subset was shown to carry infectious virus to the draining LNs (Moltedo et al, 2011).…”