We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
CD8<sup>+</sup> T cells of Listeria monocytogenes-infected mice recognize both linear and spliced proteasome products.
- Authors
Platteel, Anouk C. M.; Mishto, Michele; Textoris‐Taube, Kathrin; Keller, Christin; Liepe, Juliane; Busch, Dirk H.; Kloetzel, Peter M.; Sijts, Alice J. A. M.
- 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.
- Publication
European Journal of Immunology, 2016, Vol 46, Issue 5, p1109
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201545989