Cross-dressed dendritic cells drive memory CD8+ T-cell activation after viral infection

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Abstract

After an infection, cytotoxic T lymphocyte precursors proliferate and become effector cells by recognizing foreign peptides in the groove of major histocompatibility complex (MHC) class I molecules expressed by antigen-presenting cells (APCs)1. Professional APCs specialized for T-cell activation acquire viral antigen either by becoming infected themselves (direct presentation) or by phagocytosis of infected cells, followed by transfer of antigen to the cytosol, processing and MHC class I loading in a process referred to as cross-presentation2. An alternative way, referred to as ‘cross-dressing’, by which an uninfected APC could present antigen was postulated to be by the transfer of preformed peptide–MHC complexes from the surface of an infected cell to the APC without the need of further processing3. Here we show that this mechanism exists and boosts the antiviral response of mouse memory CD8+ T cells. A number of publications have demonstrated sharing of peptide-loaded MHC molecules in vitro4,5,6,7. Our in vitro experiments demonstrate that cross-dressing APCs do not acquire peptide–MHC complexes in the form of exosomes released by donor cells. Rather, the APCs and donor cells have to contact each other for the transfer to occur. After a viral infection, we could isolate cross-dressed APCs able to present viral antigen in vitro. Furthermore, using the diphtheria toxin system to selectively eliminate APCs that could only acquire viral peptide–MHC complexes by cross-dressing, we show that such presentation can promote the expansion of resting memory T cells. Notably, naive T cells were excluded from taking part in the response. Cross-dressing is a mechanism of antigen presentation used by dendritic cells that may have a significant role in activating previously primed CD8+ T cells.

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Figure 1: Transfer of peptide-loaded class I molecules between dendritic cells in vitro.
Figure 2: MHC I–peptide transfer does not require exosomes but does require cell contact between donor and recipient cells.
Figure 3: Dendritic cells can acquire MHC I–peptide in vivo after viral infection.
Figure 4: Cross-dressed dendritic cells in VSV-infected mice stimulate memory CD8 + T cells.

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Acknowledgements

This work was supported by the Howard Hughes Medical Institute and National Institutes of Health. L.M.W is supported by an Overseas Biomedical Fellowship from the National Health and Medical Research Council of Australia.

Author information

L.M.W. and M.J.B. devised experiments and wrote the paper. L.M.W. performed the work.

Correspondence to Michael J. Bevan.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Information

The file contains Supplementary Figures 1-10 with legend, Supplementary Methods and additional references. (PDF 673 kb)

Supplementary Movie 1

The movie shows membrane exchange between cultured DCs. DCs were labeled with either CMFDA (cytoplasmic dye - green) or Dil (membrane dye - red) and were culture together for 4 hours. Images were acquired every 4 mins. (MOV 5459 kb)

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Wakim, L., Bevan, M. Cross-dressed dendritic cells drive memory CD8+ T-cell activation after viral infection. Nature 471, 629–632 (2011) doi:10.1038/nature09863

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