Kinetics of antigen expression and epitope presentation during virus infection

Nathan Paul Croft, Stewart A Smith, Yik Chun Wong, Chor Teck Tan, Nadine Lee Dudek, Inge E A Flesch, Leon C W Lin, David C Tscharke, Anthony Wayne Purcell

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Current knowledge about the dynamics of antigen presentation to T cells during viral infection is very poor despite being of fundamental importance to our understanding of anti-viral immunity. Here we use an advanced mass spectrometry method to simultaneously quantify the presentation of eight vaccinia virus peptide-MHC complexes (epitopes) on infected cells and the amounts of their source antigens at multiple times after infection. The results show a startling 1000-fold range in abundance as well as strikingly different kinetics across the epitopes monitored. The tight correlation between onset of protein expression and epitope display for most antigens provides the strongest support to date that antigen presentation is largely linked to translation and not later degradation of antigens. Finally, we show a complete disconnect between the epitope abundance and immunodominance hierarchy of these eight epitopes. This study highlights the complexity of viral antigen presentation by the host and demonstrates the weakness of simple models that assume total protein levels are directly linked to epitope presentation and immunogenicity.
Original languageEnglish
Pages (from-to)1 - 13
Number of pages13
JournalPLoS Pathogens
Volume9
Issue number1 (Art. ID: :e1003129)
DOIs
Publication statusPublished - 2013

Cite this

Croft, N. P., Smith, S. A., Wong, Y. C., Tan, C. T., Dudek, N. L., Flesch, I. E. A., ... Purcell, A. W. (2013). Kinetics of antigen expression and epitope presentation during virus infection. PLoS Pathogens, 9(1 (Art. ID: :e1003129)), 1 - 13. https://doi.org/10.1371/journal.ppat.1003129
Croft, Nathan Paul ; Smith, Stewart A ; Wong, Yik Chun ; Tan, Chor Teck ; Dudek, Nadine Lee ; Flesch, Inge E A ; Lin, Leon C W ; Tscharke, David C ; Purcell, Anthony Wayne. / Kinetics of antigen expression and epitope presentation during virus infection. In: PLoS Pathogens. 2013 ; Vol. 9, No. 1 (Art. ID: :e1003129). pp. 1 - 13.
@article{75beb9712a3c40ec80a82f22db8e7d62,
title = "Kinetics of antigen expression and epitope presentation during virus infection",
abstract = "Current knowledge about the dynamics of antigen presentation to T cells during viral infection is very poor despite being of fundamental importance to our understanding of anti-viral immunity. Here we use an advanced mass spectrometry method to simultaneously quantify the presentation of eight vaccinia virus peptide-MHC complexes (epitopes) on infected cells and the amounts of their source antigens at multiple times after infection. The results show a startling 1000-fold range in abundance as well as strikingly different kinetics across the epitopes monitored. The tight correlation between onset of protein expression and epitope display for most antigens provides the strongest support to date that antigen presentation is largely linked to translation and not later degradation of antigens. Finally, we show a complete disconnect between the epitope abundance and immunodominance hierarchy of these eight epitopes. This study highlights the complexity of viral antigen presentation by the host and demonstrates the weakness of simple models that assume total protein levels are directly linked to epitope presentation and immunogenicity.",
author = "Croft, {Nathan Paul} and Smith, {Stewart A} and Wong, {Yik Chun} and Tan, {Chor Teck} and Dudek, {Nadine Lee} and Flesch, {Inge E A} and Lin, {Leon C W} and Tscharke, {David C} and Purcell, {Anthony Wayne}",
year = "2013",
doi = "10.1371/journal.ppat.1003129",
language = "English",
volume = "9",
pages = "1 -- 13",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "1 (Art. ID: :e1003129)",

}

Croft, NP, Smith, SA, Wong, YC, Tan, CT, Dudek, NL, Flesch, IEA, Lin, LCW, Tscharke, DC & Purcell, AW 2013, 'Kinetics of antigen expression and epitope presentation during virus infection' PLoS Pathogens, vol. 9, no. 1 (Art. ID: :e1003129), pp. 1 - 13. https://doi.org/10.1371/journal.ppat.1003129

Kinetics of antigen expression and epitope presentation during virus infection. / Croft, Nathan Paul; Smith, Stewart A; Wong, Yik Chun; Tan, Chor Teck; Dudek, Nadine Lee; Flesch, Inge E A; Lin, Leon C W; Tscharke, David C; Purcell, Anthony Wayne.

In: PLoS Pathogens, Vol. 9, No. 1 (Art. ID: :e1003129), 2013, p. 1 - 13.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Kinetics of antigen expression and epitope presentation during virus infection

AU - Croft, Nathan Paul

AU - Smith, Stewart A

AU - Wong, Yik Chun

AU - Tan, Chor Teck

AU - Dudek, Nadine Lee

AU - Flesch, Inge E A

AU - Lin, Leon C W

AU - Tscharke, David C

AU - Purcell, Anthony Wayne

PY - 2013

Y1 - 2013

N2 - Current knowledge about the dynamics of antigen presentation to T cells during viral infection is very poor despite being of fundamental importance to our understanding of anti-viral immunity. Here we use an advanced mass spectrometry method to simultaneously quantify the presentation of eight vaccinia virus peptide-MHC complexes (epitopes) on infected cells and the amounts of their source antigens at multiple times after infection. The results show a startling 1000-fold range in abundance as well as strikingly different kinetics across the epitopes monitored. The tight correlation between onset of protein expression and epitope display for most antigens provides the strongest support to date that antigen presentation is largely linked to translation and not later degradation of antigens. Finally, we show a complete disconnect between the epitope abundance and immunodominance hierarchy of these eight epitopes. This study highlights the complexity of viral antigen presentation by the host and demonstrates the weakness of simple models that assume total protein levels are directly linked to epitope presentation and immunogenicity.

AB - Current knowledge about the dynamics of antigen presentation to T cells during viral infection is very poor despite being of fundamental importance to our understanding of anti-viral immunity. Here we use an advanced mass spectrometry method to simultaneously quantify the presentation of eight vaccinia virus peptide-MHC complexes (epitopes) on infected cells and the amounts of their source antigens at multiple times after infection. The results show a startling 1000-fold range in abundance as well as strikingly different kinetics across the epitopes monitored. The tight correlation between onset of protein expression and epitope display for most antigens provides the strongest support to date that antigen presentation is largely linked to translation and not later degradation of antigens. Finally, we show a complete disconnect between the epitope abundance and immunodominance hierarchy of these eight epitopes. This study highlights the complexity of viral antigen presentation by the host and demonstrates the weakness of simple models that assume total protein levels are directly linked to epitope presentation and immunogenicity.

UR - http://www.plospathogens.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.ppat.1003129&representation=PDF

U2 - 10.1371/journal.ppat.1003129

DO - 10.1371/journal.ppat.1003129

M3 - Article

VL - 9

SP - 1

EP - 13

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 1 (Art. ID: :e1003129)

ER -

Croft NP, Smith SA, Wong YC, Tan CT, Dudek NL, Flesch IEA et al. Kinetics of antigen expression and epitope presentation during virus infection. PLoS Pathogens. 2013;9(1 (Art. ID: :e1003129)):1 - 13. https://doi.org/10.1371/journal.ppat.1003129