title: CD8(+) T cells of Listeria monocytogenes-infected mice recognize both linear and spliced proteasome products.
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-2K(b) -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-2K(b) binding affinity. These spliced peptides, which displayed sequence similarity with LLO296-304 , bound to H-2K(b) 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.
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Anouk C M
authors.initials: AC
authors.lastname: Platteel
authors.affiliation: Institut für Biochemie, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Interdepartmental Centre "Luigi Galvani" for Bioinformatics, Biophysics and Biocomplexity (CIG), Alma Mater Studiorum, University of Bologna, Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Mishto
authors.affiliation: Institut für Biochemie, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Textoris-Taube
authors.affiliation: Institut für Biochemie, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Keller
authors.affiliation: Centre for Integrative Systems Biology and Bioinformatics, Department of Life Sciences, Imperial College London, London, UK.
authors.forename: Juliane
authors.initials: J
authors.lastname: Liepe
authors.affiliation: Institute for Medical Microbiology, Immunology and Hygiene, TU Munich, Munich, Germany.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.affiliation: Institut für Biochemie, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Kloetzel
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Alice J A M
authors.initials: AJ
authors.lastname: Sijts
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003198:Computer Simulation; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D057131:Immune Evasion; D008089:Listeria monocytogenes / Q000737:chemistry / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D013058:Mass Spectrometry; D051379:Mice; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D019154:Protein Splicing
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D046988:Proteasome Endopeptidase Complex
keywords: CD8+ T cells; Listeria monocytogenes; MHC class I antigen processing; Proteasome; Proteasome-catalyzed peptide splicing