CD8+ T cell responses to viral infection
are driven by the presentation of peptide epitopes on the surface of cells in
the context of major histocompatibility (MHC) class I complexes. Despite a
thorough understanding of MHC antigen processing and presentation during viral
infection, there is a lack of knowledge relating to the relative kinetics of
MHC-peptide presentation from across a viral proteome. This is especially
relevant for large viruses with ordered cascades of gene expression. In this
context vaccinia virus (VACV) is an ideal model, with a well characterised CD8+
T cell epitope hierarcy in mice that includes antigens from all kinetic classes
of virus genes. The abundance of 17 VACV MHC-peptide complexes were quantified
in parallel using mass spectrometric methods at multiple times over 12 hours of
infection. Furthermore, levels of source proteins
for each peptide were simultaneously measured and related to MHC-peptide
levels. Finally, the biochemical data were related to the known immunodomince
of the epitopes. Our results represent the first multi-epitope study
quantifying MHC presentation of viral epitopes during infection and provide
important insights into the kinetics of viral epitope display. Further, they
show that antigen presentation during VACV infection is more complex than has
been suggested by previous studies and that there is no simple relationship
between peptide presentation levels and immunodominance across that viral
proteome.