Quantification of epitope abundance reveals the effect of direct and cross-presentation on influenza CTL responses

Nat Commun. 2019 Jun 28;10(1):2846. doi: 10.1038/s41467-019-10661-8.


The magnitude of T cell responses to infection is a function of the naïve T cell repertoire combined with the context and duration of antigen presentation. Using mass spectrometry, we identify and quantify 21 class 1 MHC-restricted influenza A virus (IAV)-peptides following either direct or cross-presentation. All these peptides, including seven novel epitopes, elicit T cell responses in infected C57BL/6 mice. Directly presented IAV epitopes maintain their relative abundance across distinct cell types and reveal a broad range of epitope abundances. In contrast, cross-presented epitopes are more uniform in abundance. We observe a clear disparity in the abundance of the two key immunodominant IAV antigens, wherein direct infection drives optimal nucleoprotein (NP)366-374 presentation, while cross-presentation is optimal for acid polymerase (PA)224-233 presentation. The study demonstrates how assessment of epitope abundance in both modes of antigen presentation is necessary to fully understand the immunogenicity and response magnitude to T cell epitopes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / physiology*
  • Cell Line
  • Epitopes, T-Lymphocyte / immunology
  • Epitopes, T-Lymphocyte / physiology*
  • Humans
  • Influenza A virus / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Biological
  • Multivariate Analysis
  • Orthomyxoviridae Infections / immunology*
  • Orthomyxoviridae Infections / virology
  • T-Lymphocytes, Cytotoxic / physiology*


  • Epitopes, T-Lymphocyte