CD8+ T cells of Listeria monocytogenes-infected mice recognize both linear and spliced proteasome products

Anouk C.M. Platteel, Michele Mishto, Kathrin Textoris-Taube, Christin Keller, Juliane Liepe, Dirk H. Busch, Peter M. Kloetzel, Alice J.A.M. Sijts

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

CD8+ T cells responding to infection recognize pathogen-derived epitopes presented by MHC class-I molecules. While most of such epitopes are generated by proteasome-mediated antigen cleavage, analysis of tumor antigen processing has revealed that epitopes may also derive from proteasome-catalyzed peptide splicing (PCPS). To determine whether PCPS contributes to epitope processing during infection, we analyzed the fragments produced by purified proteasomes from a Listeria monocytogenes polypeptide. Mass spectrometry identified a known H-2Kb-presented linear epitope (LLO296-304) in the digests, as well as four spliced peptides that were trimmed by ERAP into peptides with in silico predicted H-2Kb binding affinity. These spliced peptides, which displayed sequence similarity with LLO296-304, bound to H-2Kb molecules in cellular assays and one of the peptides was recognized by CD8+ T cells of infected mice. This spliced epitope differed by one amino acid from LLO296-304 and double staining with LLO296-304- and spliced peptide-folded MHC multimers showed that LLO296-304 and its spliced variant were recognized by the same CD8+ T cells. Thus, PCPS multiplies the variety of peptides that is processed from an antigen and leads to the production of epitope variants that can be recognized by cross-reacting pathogen-specific CD8+ T cells. Such mechanism may reduce the chances for pathogen immune evasion.

Original languageEnglish
Pages (from-to)1109-1118
Number of pages10
JournalEuropean Journal of Immunology
Volume46
Issue number5
DOIs
StatePublished - 1 May 2016

Keywords

  • CD8 T cells
  • Listeria monocytogenes
  • MHC class I antigen processing
  • Proteasome
  • Proteasome-catalyzed peptide splicing

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