title: The cellular redox environment alters antigen presentation.
abstract: Cysteine-containing peptides represent an important class of T cell epitopes, yet their prevalence remains underestimated. We have established and interrogated a database of around 70,000 naturally processed MHC-bound peptides and demonstrate that cysteine-containing peptides are presented on the surface of cells in an MHC allomorph-dependent manner and comprise on average 5-10% of the immunopeptidome. A significant proportion of these peptides are oxidatively modified, most commonly through covalent linkage with the antioxidant glutathione. Unlike some of the previously reported cysteine-based modifications, this represents a true physiological alteration of cysteine residues. Furthermore, our results suggest that alterations in the cellular redox state induced by viral infection are communicated to the immune system through the presentation of S-glutathionylated viral peptides, resulting in altered T cell recognition. Our data provide a structural basis for how the glutathione modification alters recognition by virus-specific T cells. Collectively, these results suggest that oxidative stress represents a mechanism for modulating the virus-specific T cell response.
authors.affiliation: From the Department of Microbiology and the Interdisciplinary Program in Immunology, University of Iowa, Iowa City, Iowa 52242.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Trujillo
authors.affiliation: the Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia, the Department of Biochemistry and Molecular Biology and.
authors.forename: Nathan P
authors.initials: NP
authors.lastname: Croft
authors.affiliation: the Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia, the Department of Biochemistry and Molecular Biology and.
authors.forename: Nadine L
authors.initials: NL
authors.lastname: Dudek
authors.affiliation: From the Department of Microbiology and.
authors.forename: Rudragouda
authors.initials: R
authors.lastname: Channappanavar
authors.affiliation: the Department of Biochemistry and Molecular Biology and.
authors.forename: Alex
authors.initials: A
authors.lastname: Theodossis
authors.affiliation: the Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Andrew I
authors.initials: AI
authors.lastname: Webb
authors.affiliation: the Department of Biochemistry and Molecular Biology and.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Dunstone
authors.affiliation: the Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Patricia T
authors.initials: PT
authors.lastname: Illing
authors.affiliation: From the Department of Microbiology and the Research School of Biology, Australian National University, Canberra, Australian Capital Territory 0200, Australia, and.
authors.forename: Noah S
authors.initials: NS
authors.lastname: Butler
authors.affiliation: From the Department of Microbiology and.
authors.forename: Craig
authors.initials: C
authors.lastname: Fett
authors.affiliation: Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: David C
authors.initials: DC
authors.lastname: Tscharke
authors.affiliation: the Department of Biochemistry and Molecular Biology and Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia, the Institute of Infection and Immunity, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom.
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.affiliation: From the Department of Microbiology and the Interdisciplinary Program in Immunology, University of Iowa, Iowa City, Iowa 52242, Stanley-perlman@uiowa.edu.
authors.forename: Stanley
authors.initials: S
authors.lastname: Perlman
authors.affiliation: the Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia, the Department of Biochemistry and Molecular Biology and anthony.purcell@monash.edu.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018352:Coronavirus Infections / Q000276:immunology / Q000378:metabolism / Q000662:veterinary* / Q000821:virology; D003545:Cysteine / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000235:genetics / Q000276:immunology*; D010084:Oxidation-Reduction; D012376:Rodent Diseases / Q000276:immunology / Q000378:metabolism* / Q000821:virology
chemical_list: D018984:Epitopes, T-Lymphocyte; D005978:Glutathione; D003545:Cysteine
keywords: Antigen Presentation; Antigen Processing; Glutathionylation; Mass Spectrometry (MS); Oxidation-Reduction (Redox); Redox Regulation; T-cell; Viral Immunology