Can cross-dressing kill viruses?

Edward Carr, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP

How do professional antigen presenting cells (such as dendritic cells) present peptides derived from intracellular pathogens on MHC class I?  One method is for the antigen presenting cell (APC) to be infected by the pathogen.  Unsurprisingly, there are a large number of pathogens that do not infect APCs, avoiding such straightforward immunosurveillance.  This escape route is covered by a process called ‘cross-presentation’ – pathogenic material is delivered to the APC (by phagocytosis or other means) and diverted into a pathway that loads MHC class I molecules for presentation to CD8 T cells.  In this week’s Nature, Wakim and Bevan describe a phenomenon called ‘cross-dressing’ characterised by the transfer of MHC class I molecules pre-loaded with antigenic peptide from the infected cell to the antigen presenting cell (APC) without further processing (1).

Beginning with some in vitro work, Wakim and Bevan demonstrate that formed peptide-MHC class I can be transferred between APC populations.  This is also successful using ‘recipient’ APC that are deficient in a gene required cross-presentation, suggesting that cross-dressing really does underpin their results, rather than ‘leaking’ of antigen in the petri dish.  Similar in vitro experiments demonstrated that cell-cell contact was required for cross-dressing to occur.

Cross-dressing is shown – in later experiments – to occur in vivo in response to an intracellular viral infection.  The CD8 T cell population that proliferates in response to cross-dressed APC is a memory population (a population of T cells that have already encountered their cognate peptide-MHC).  Cross-dressing therefore allows re-activation of virus-specific T cells without the need for antigen processing by APCs, permitting a rapid CD8 T cell response to re-infection with the same intracellular pathogen.

This study provides evidence to support a novel mechanism for CD8 T cell re-activation.  Whether cross-dressing is a universal feature of all intracellular infections is unknown.  To pose the question differently – how promiscuous are cross-dressing APCs?  If cross-dressing APCs is a common feature of CD8 T cell re-activation, it could provide an alternative approach for booster vaccination. 

References: 

1. Wakim LM, Bevan MJ. Cross-dressed dendritic cells drive memory CD8+ T-cell activation after viral infection. Nature 2011 Mar;471(7340):629-632.
doi: 10.1038/nature09863