Dataset Information

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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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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Project description:Miao2010 - Innate and adaptive immune responses to primary Influenza A Virus infection This model is described in the article: Quantifying the early immune response and adaptive immune response kinetics in mice infected with influenza A virus. Miao H, Hollenbaugh JA, Zand MS, Holden-Wiltse J, Mosmann TR, Perelson AS, Wu H, Topham DJ. J. Virol. 2010 Jul; 84(13): 6687-6698 Abstract: Seasonal and pandemic influenza A virus (IAV) continues to be a public health threat. However, we lack a detailed and quantitative understanding of the immune response kinetics to IAV infection and which biological parameters most strongly influence infection outcomes. To address these issues, we use modeling approaches combined with experimental data to quantitatively investigate the innate and adaptive immune responses to primary IAV infection. Mathematical models were developed to describe the dynamic interactions between target (epithelial) cells, influenza virus, cytotoxic T lymphocytes (CTLs), and virus-specific IgG and IgM. IAV and immune kinetic parameters were estimated by fitting models to a large data set obtained from primary H3N2 IAV infection of 340 mice. Prior to a detectable virus-specific immune response (before day 5), the estimated half-life of infected epithelial cells is approximately 1.2 days, and the half-life of free infectious IAV is approximately 4 h. During the adaptive immune response (after day 5), the average half-life of infected epithelial cells is approximately 0.5 days, and the average half-life of free infectious virus is approximately 1.8 min. During the adaptive phase, model fitting confirms that CD8(+) CTLs are crucial for limiting infected cells, while virus-specific IgM regulates free IAV levels. This may imply that CD4 T cells and class-switched IgG antibodies are more relevant for generating IAV-specific memory and preventing future infection via a more rapid secondary immune response. Also, simulation studies were performed to understand the relative contributions of biological parameters to IAV clearance. This study provides a basis to better understand and predict influenza virus immunity. This model is hosted on BioModels Database and identified by: BIOMD0000000546. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

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

Publications

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

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