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Journal Article

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


Liepe,  J.
Research Group of Quantitative and System Biology, MPI for Biophysical Chemistry, Max Planck Society;

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(Supplementary material), 681KB

(Supplementary material), 681KB


Platteel, A. C. M., Mishto, M., Textoris-Taube, K., Keller, C., Liepe, J., Busch, D. H., et al. (2016). CD8(+) T cells of Listeria monocytogenes-infected mice recognize both linear and spliced proteasome products. European Journal of Immunology, 46(5), 1109-1118. doi:10.1002/eji.201545989.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002D-FE17-E
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.