The cellular redox environment alters antigen presentation

Jonathan A Trujillo; Nathan P Croft; Nadine L Dudek; Rudragouda Channappanavar; Alex Theodossis; Andrew I Webb; Michelle A Dunstone; Patricia T Illing; Noah S Butler; Craig Fett; David C Tscharke; Jamie Rossjohn; Stanley Perlman; Anthony W Purcell

doi:10.1074/jbc.M114.573402

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The cellular redox environment alters antigen presentation

Journal article

Open access

Peer reviewed

The cellular redox environment alters antigen presentation

Jonathan A Trujillo, Nathan P Croft, Nadine L Dudek, Rudragouda Channappanavar, Alex Theodossis, Andrew I Webb, Michelle A Dunstone, Patricia T Illing, Noah S Butler, Craig Fett, …

The Journal of biological chemistry, Vol.289(40), pp.27979-27991

10/03/2014

DOI: 10.1074/jbc.M114.573402

PMCID: PMC4183829

PMID: 25135637

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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.

Glutathione - metabolism

Brain - virology

Epitopes, T-Lymphocyte - genetics

Male

Brain - metabolism

Murine hepatitis virus - immunology

Coronavirus Infections - metabolism

Antigen Presentation

Female

Cysteine - metabolism

Epitopes, T-Lymphocyte - immunology

Oxidation-Reduction

Mice, Inbred C57BL

Rodent Diseases - immunology

Rodent Diseases - virology

Coronavirus Infections - immunology

Animals

Coronavirus Infections - veterinary

Coronavirus Infections - virology

Rodent Diseases - metabolism

Mice

CD8-Positive T-Lymphocytes - immunology

Brain - immunology

Epitopes, T-Lymphocyte - metabolism

Murine hepatitis virus - genetics

Details

Title: Subtitle: The cellular redox environment alters antigen presentation
Creators: Jonathan A Trujillo - From the Department of Microbiology and the Interdisciplinary Program in Immunology, University of Iowa, Iowa City, Iowa 52242
Nathan P Croft - 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
Nadine L Dudek - 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
Rudragouda Channappanavar - From the Department of Microbiology and
Alex Theodossis - the Department of Biochemistry and Molecular Biology and
Andrew I Webb - the Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia
Michelle A Dunstone - the Department of Biochemistry and Molecular Biology and
Patricia T Illing - the Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia
Noah S Butler - From the Department of Microbiology and the Research School of Biology, Australian National University, Canberra, Australian Capital Territory 0200, Australia, and
Craig Fett - From the Department of Microbiology and
David C Tscharke - Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia
Jamie Rossjohn - 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
Stanley Perlman - From the Department of Microbiology and the Interdisciplinary Program in Immunology, University of Iowa, Iowa City, Iowa 52242, Stanley-perlman@uiowa.edu
Anthony W Purcell - 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
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.289(40), pp.27979-27991
DOI: 10.1074/jbc.M114.573402
PMID: 25135637
PMCID: PMC4183829
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: T32 GM007337 / NIGMS NIH HHS R01 NS036592 / NINDS NIH HHS
Language: English
Date published: 10/03/2014
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777472002771

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