Most viral peptides displayed by class I MHC on infected cells are immunogenic

Nathan P. Croft, Stewart A. Smith, Jana Pickering, John Sidney, Bjoern Peters, Pouya Faridi, Matthew J. Witney, Prince Sebastian, Inge E.A. Flesch, Sally L. Heading, Alessandro Sette, Nicole L. La Gruta, Anthony W. Purcell, David C. Tscharke

Research output: Contribution to journalArticleResearchpeer-review

Abstract

CD8 + T cells are essential effectors in antiviral immunity, recognizing short virus-derived peptides presented by MHC class I (pMHCI) on the surface of infected cells. However, the fraction of viral pMHCI on infected cells that are immunogenic has not been shown for any virus. To approach this fundamental question, we used peptide sequencing by high-resolution mass spectrometry to identify more than 170 vaccinia virus pMHCI presented on infected mouse cells. Next, we screened each peptide for immunogenicity in multiple virus-infected mice, revealing a wide range of immu-nogenicities. A surprisingly high fraction (>80%) of pMHCI were immunogenic in at least one infected mouse, and nearly 40% were immunogenic across more than half of the mice screened. The high number of peptides found to be immunogenic and the distribution of responses across mice give us insight into the specificity of antiviral CD8 + T cell responses.

Original languageEnglish
Pages (from-to)3112-3117
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number8
DOIs
Publication statusPublished - 19 Feb 2019

Keywords

  • Antigen presentation
  • CD8 T cells
  • MHC class I
  • Vaccinia virus
  • Virus

Cite this

Croft, Nathan P. ; Smith, Stewart A. ; Pickering, Jana ; Sidney, John ; Peters, Bjoern ; Faridi, Pouya ; Witney, Matthew J. ; Sebastian, Prince ; Flesch, Inge E.A. ; Heading, Sally L. ; Sette, Alessandro ; La Gruta, Nicole L. ; Purcell, Anthony W. ; Tscharke, David C. / Most viral peptides displayed by class I MHC on infected cells are immunogenic. In: Proceedings of the National Academy of Sciences of the United States of America. 2019 ; Vol. 116, No. 8. pp. 3112-3117.
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title = "Most viral peptides displayed by class I MHC on infected cells are immunogenic",
abstract = "CD8 + T cells are essential effectors in antiviral immunity, recognizing short virus-derived peptides presented by MHC class I (pMHCI) on the surface of infected cells. However, the fraction of viral pMHCI on infected cells that are immunogenic has not been shown for any virus. To approach this fundamental question, we used peptide sequencing by high-resolution mass spectrometry to identify more than 170 vaccinia virus pMHCI presented on infected mouse cells. Next, we screened each peptide for immunogenicity in multiple virus-infected mice, revealing a wide range of immu-nogenicities. A surprisingly high fraction (>80{\%}) of pMHCI were immunogenic in at least one infected mouse, and nearly 40{\%} were immunogenic across more than half of the mice screened. The high number of peptides found to be immunogenic and the distribution of responses across mice give us insight into the specificity of antiviral CD8 + T cell responses.",
keywords = "Antigen presentation, CD8 T cells, MHC class I, Vaccinia virus, Virus",
author = "Croft, {Nathan P.} and Smith, {Stewart A.} and Jana Pickering and John Sidney and Bjoern Peters and Pouya Faridi and Witney, {Matthew J.} and Prince Sebastian and Flesch, {Inge E.A.} and Heading, {Sally L.} and Alessandro Sette and {La Gruta}, {Nicole L.} and Purcell, {Anthony W.} and Tscharke, {David C.}",
year = "2019",
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doi = "10.1073/pnas.1815239116",
language = "English",
volume = "116",
pages = "3112--3117",
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Croft, NP, Smith, SA, Pickering, J, Sidney, J, Peters, B, Faridi, P, Witney, MJ, Sebastian, P, Flesch, IEA, Heading, SL, Sette, A, La Gruta, NL, Purcell, AW & Tscharke, DC 2019, 'Most viral peptides displayed by class I MHC on infected cells are immunogenic', Proceedings of the National Academy of Sciences of the United States of America, vol. 116, no. 8, pp. 3112-3117. https://doi.org/10.1073/pnas.1815239116

Most viral peptides displayed by class I MHC on infected cells are immunogenic. / Croft, Nathan P.; Smith, Stewart A.; Pickering, Jana; Sidney, John; Peters, Bjoern; Faridi, Pouya; Witney, Matthew J.; Sebastian, Prince; Flesch, Inge E.A.; Heading, Sally L.; Sette, Alessandro; La Gruta, Nicole L.; Purcell, Anthony W.; Tscharke, David C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, No. 8, 19.02.2019, p. 3112-3117.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Most viral peptides displayed by class I MHC on infected cells are immunogenic

AU - Croft, Nathan P.

AU - Smith, Stewart A.

AU - Pickering, Jana

AU - Sidney, John

AU - Peters, Bjoern

AU - Faridi, Pouya

AU - Witney, Matthew J.

AU - Sebastian, Prince

AU - Flesch, Inge E.A.

AU - Heading, Sally L.

AU - Sette, Alessandro

AU - La Gruta, Nicole L.

AU - Purcell, Anthony W.

AU - Tscharke, David C.

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AB - CD8 + T cells are essential effectors in antiviral immunity, recognizing short virus-derived peptides presented by MHC class I (pMHCI) on the surface of infected cells. However, the fraction of viral pMHCI on infected cells that are immunogenic has not been shown for any virus. To approach this fundamental question, we used peptide sequencing by high-resolution mass spectrometry to identify more than 170 vaccinia virus pMHCI presented on infected mouse cells. Next, we screened each peptide for immunogenicity in multiple virus-infected mice, revealing a wide range of immu-nogenicities. A surprisingly high fraction (>80%) of pMHCI were immunogenic in at least one infected mouse, and nearly 40% were immunogenic across more than half of the mice screened. The high number of peptides found to be immunogenic and the distribution of responses across mice give us insight into the specificity of antiviral CD8 + T cell responses.

KW - Antigen presentation

KW - CD8 T cells

KW - MHC class I

KW - Vaccinia virus

KW - Virus

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DO - 10.1073/pnas.1815239116

M3 - Article

VL - 116

SP - 3112

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JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

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