Kinetics of antigen expression and epitope presentation during virus infection

PLoS Pathog. 2013 Jan;9(1):e1003129. doi: 10.1371/journal.ppat.1003129. Epub 2013 Jan 31.

Abstract

Current knowledge about the dynamics of antigen presentation to T cells during viral infection is very poor despite being of fundamental importance to our understanding of anti-viral immunity. Here we use an advanced mass spectrometry method to simultaneously quantify the presentation of eight vaccinia virus peptide-MHC complexes (epitopes) on infected cells and the amounts of their source antigens at multiple times after infection. The results show a startling 1000-fold range in abundance as well as strikingly different kinetics across the epitopes monitored. The tight correlation between onset of protein expression and epitope display for most antigens provides the strongest support to date that antigen presentation is largely linked to translation and not later degradation of antigens. Finally, we show a complete disconnect between the epitope abundance and immunodominance hierarchy of these eight epitopes. This study highlights the complexity of viral antigen presentation by the host and demonstrates the weakness of simple models that assume total protein levels are directly linked to epitope presentation and immunogenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigen-Presenting Cells / immunology*
  • Cell Line
  • Dendritic Cells / immunology
  • Dendritic Cells / virology
  • Epitope Mapping
  • Epitopes / immunology*
  • Host-Pathogen Interactions
  • Kinetics
  • Major Histocompatibility Complex / immunology
  • Mass Spectrometry
  • Mice
  • Smallpox / immunology*
  • Vaccinia virus / immunology*
  • Viral Proteins / chemistry
  • Viral Proteins / immunology
  • Virus Diseases / immunology*

Substances

  • Epitopes
  • Viral Proteins

Grant support

This work was funded by a Project Grant for the National Health and Medical Research Council of Australia (NH&MRC) project grant 1023141 and an Early Career Research grant from the University of Melbourne to N.P.C. This work was supported by infrastructure obtained through an Australian Research Council (ARC) Linkage Infrastructure and Equipment Grant (LE100100036). A.W.P. is an NHMRC Senior Research Fellow. D.C.T. is an ARC Future Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.