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Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):3112-3117. doi: 10.1073/pnas.1815239116. Epub 2019 Feb 4.

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

Author information

1
Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia; nathan.croft@monash.edu anthony.purcell@monash.edu david.tscharke@anu.edu.au.
2
Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
3
John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia.
4
Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
5
Department of Medicine, University of California, San Diego, La Jolla, CA 92093.
6
Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
7
Department of Microbiology and Immunology, University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
8
John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia; nathan.croft@monash.edu anthony.purcell@monash.edu david.tscharke@anu.edu.au.

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 immunogenicities. 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:

CD8+ T cells; MHC class I; antigen presentation; vaccinia virus; virus

PMID:
30718433
PMCID:
PMC6386720
DOI:
10.1073/pnas.1815239116
[Indexed for MEDLINE]
Free PMC Article

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