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 TT Illing, Noah S Butler, Craig Fett, David C Tscharke, Jamie Rossjohn, Stanley Perlman, Anthony W Purcell

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Pages (from-to)27979 - 27991
Number of pages13
JournalJournal of Biological Chemistry
Volume289
Issue number40
DOIs
Publication statusPublished - 2014

Cite this

Trujillo, J. A., Croft, N. P., Dudek, N. L., Channappanavar, R., Theodossis, A., Webb, A. I., ... Purcell, A. W. (2014). The cellular redox environment alters antigen presentation. Journal of Biological Chemistry, 289(40), 27979 - 27991. https://doi.org/10.1074/jbc.M114.573402
Trujillo, Jonathan A ; Croft, Nathan P ; Dudek, Nadine L ; Channappanavar, Rudragouda ; Theodossis, Alex ; Webb, Andrew I ; Dunstone, Michelle A ; Illing, Patricia TT ; Butler, Noah S ; Fett, Craig ; Tscharke, David C ; Rossjohn, Jamie ; Perlman, Stanley ; Purcell, Anthony W. / The cellular redox environment alters antigen presentation. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 40. pp. 27979 - 27991.
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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.",
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Trujillo, JA, Croft, NP, Dudek, NL, Channappanavar, R, Theodossis, A, Webb, AI, Dunstone, MA, Illing, PTT, Butler, NS, Fett, C, Tscharke, DC, Rossjohn, J, Perlman, S & Purcell, AW 2014, 'The cellular redox environment alters antigen presentation', Journal of Biological Chemistry, vol. 289, no. 40, pp. 27979 - 27991. https://doi.org/10.1074/jbc.M114.573402

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 TT; Butler, Noah S; Fett, Craig; Tscharke, David C; Rossjohn, Jamie; Perlman, Stanley; Purcell, Anthony W.

In: Journal of Biological Chemistry, Vol. 289, No. 40, 2014, p. 27979 - 27991.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Trujillo, Jonathan A

AU - Croft, Nathan P

AU - Dudek, Nadine L

AU - Channappanavar, Rudragouda

AU - Theodossis, Alex

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AU - Dunstone, Michelle A

AU - Illing, Patricia TT

AU - Butler, Noah S

AU - Fett, Craig

AU - Tscharke, David C

AU - Rossjohn, Jamie

AU - Perlman, Stanley

AU - Purcell, Anthony W

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AB - 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.

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Trujillo JA, Croft NP, Dudek NL, Channappanavar R, Theodossis A, Webb AI et al. The cellular redox environment alters antigen presentation. Journal of Biological Chemistry. 2014;289(40):27979 - 27991. https://doi.org/10.1074/jbc.M114.573402