Kinetics of antigen expression and epitope presentation during virus infection.
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 vacci...
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2013
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oai:doaj.org-article:6a1915d21ff04a768d317385c5da648c2021-11-18T06:06:06ZKinetics of antigen expression and epitope presentation during virus infection.1553-73661553-737410.1371/journal.ppat.1003129https://doaj.org/article/6a1915d21ff04a768d317385c5da648c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23382674/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Current 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.Nathan P CroftStewart A SmithYik Chun WongChor Teck TanNadine L DudekInge E A FleschLeon C W LinDavid C TscharkeAnthony W PurcellPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 1, p e1003129 (2013) |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
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Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Nathan P Croft Stewart A Smith Yik Chun Wong Chor Teck Tan Nadine L Dudek Inge E A Flesch Leon C W Lin David C Tscharke Anthony W Purcell Kinetics of antigen expression and epitope presentation during virus infection. |
description |
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. |
format |
article |
author |
Nathan P Croft Stewart A Smith Yik Chun Wong Chor Teck Tan Nadine L Dudek Inge E A Flesch Leon C W Lin David C Tscharke Anthony W Purcell |
author_facet |
Nathan P Croft Stewart A Smith Yik Chun Wong Chor Teck Tan Nadine L Dudek Inge E A Flesch Leon C W Lin David C Tscharke Anthony W Purcell |
author_sort |
Nathan P Croft |
title |
Kinetics of antigen expression and epitope presentation during virus infection. |
title_short |
Kinetics of antigen expression and epitope presentation during virus infection. |
title_full |
Kinetics of antigen expression and epitope presentation during virus infection. |
title_fullStr |
Kinetics of antigen expression and epitope presentation during virus infection. |
title_full_unstemmed |
Kinetics of antigen expression and epitope presentation during virus infection. |
title_sort |
kinetics of antigen expression and epitope presentation during virus infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doaj.org/article/6a1915d21ff04a768d317385c5da648c |
work_keys_str_mv |
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