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The majority of viral peptides displayed on class I MHC are immunogenic during infection

ABSTRACT: CD8+ T cells are essential effectors in anti-viral immunity, recognising 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 nearly 200 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 immunogenicities. A surprisingly high fraction (>80%) of pMHCI were immunogenic at least one infected animal and around half of these were dominant, which we define as being immunogenic across more than half of the mice screened. The high number of peptides found to be immunogenic and the variability in immunogenicity across mice give us new insight into the specificity of anti-viral CD8+ T cell responses.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Vaccinia Virus Wr Mus Musculus (mouse)

TISSUE(S): Dendritic Cell, Cell Culture

SUBMITTER: Nathan Croft

LAB HEAD: Anthony Purcell

PROVIDER: PXD010811 | Pride | 2019-01-23

REPOSITORIES: Pride

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			Action	DRS
	A10Dec112011NathanVACV6hrKbY3.wiff	Wiff
	A10Dec112011NathanVACV6hrKbY3.wiff.mtd	Wiff
	A10Dec112011NathanVACV6hrKbY3.wiff.scan	Wiff
	A10Feb22012NathanVACV6hrDbexcl.wiff	Wiff
	A10Feb22012NathanVACV6hrDbexcl.wiff.mtd	Wiff

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

Croft Nathan P NP Smith Stewart A SA Pickering Jana J Sidney John J Peters Bjoern B Faridi Pouya P Witney Matthew J MJ Sebastian Prince P Flesch Inge E A IEA Heading Sally L SL Sette Alessandro A La Gruta Nicole L NL Purcell Anthony W AW Tscharke David C DC

Proceedings of the National Academy of Sciences of the United States of America 20190204 8

CD8<sup>+</sup> 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 pep ...[more]

PMID: 30718433

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