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The cellular redox environment alters antigen presentation

Trujillo, Jonathan A., Croft, Nathan P., Dudek, Nadine L., Channappanavar, Rudragouda, Theodossis, Alex, Webb, Andrew I., Dunstone, Michelle A., Illing, Patricia T., Butler, Noah S., Fett, Craig, Tscharke, David C., Rossjohn, Jamie, Perlman, Stanley and Purcell, Anthony W. 2014. The cellular redox environment alters antigen presentation. The Journal of Biological Chemistry 289 (40) , pp. 27979-91. 10.1074/jbc.M114.573402

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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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: antigen presentation; antigen processing; glutathionylation; mass spectrometry (MS); oxidation-reduction (redox); redox regulation; T-cell; viral immunology
Publisher: American Society for Biochemistry and Molecular Biology
ISSN: 1083-351X
Date of Acceptance: 18 August 2014
Last Modified: 04 Jun 2017 09:07
URI: http://orca-mwe.cf.ac.uk/id/eprint/90732

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