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Identification of Class I HLA T Cell Control Epitopes for West Nile Virus

Kaabinejadian, S and Piazza, PA and McMurtrey, CP and Vernon, SR and Cate, SJ and Bardet, W and Schafer, FB and Jackson, KW and Campbell, DM and Buchli, R and Rinaldo, CR and Hildebrand, WH (2013) Identification of Class I HLA T Cell Control Epitopes for West Nile Virus. PLoS ONE, 8 (6).

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Abstract

The recent West Nile virus (WNV) outbreak in the United States underscores the importance of understanding human immune responses to this pathogen. Via the presentation of viral peptide ligands at the cell surface, class I HLA mediate the T cell recognition and killing of WNV infected cells. At this time, there are two key unknowns in regards to understanding protective T cell immunity: 1) the number of viral ligands presented by the HLA of infected cells, and 2) the distribution of T cell responses to these available HLA/viral complexes. Here, comparative mass spectroscopy was applied to determine the number of WNV peptides presented by the HLA-A*11:01 of infected cells after which T cell responses to these HLA/WNV complexes were assessed. Six viral peptides derived from capsid, NS3, NS4b, and NS5 were presented. When T cells from infected individuals were tested for reactivity to these six viral ligands, polyfunctional T cells were focused on the GTL9 WNV capsid peptide, ligands from NS3, NS4b, and NS5 were less immunogenic, and two ligands were largely inert, demonstrating that class I HLA reduce the WNV polyprotein to a handful of immune targets and that polyfunctional T cells recognize infections by zeroing in on particular HLA/WNV epitopes. Such dominant HLA/peptide epitopes are poised to drive the development of WNV vaccines that elicit protective T cells as well as providing key antigens for immunoassays that establish correlates of viral immunity. © 2013 Kaabinejadian et al.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Kaabinejadian, S
Piazza, PApaolo@pitt.eduPAOLO
McMurtrey, CP
Vernon, SR
Cate, SJ
Bardet, W
Schafer, FB
Jackson, KW
Campbell, DM
Buchli, R
Rinaldo, CRRINALDO@pitt.eduRINALDO
Hildebrand, WH
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorWang, TianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 10 June 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 6
DOI or Unique Handle: 10.1371/journal.pone.0066298
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
School of Medicine > Pathology
Refereed: Yes
Date Deposited: 15 Jul 2013 20:17
Last Modified: 02 Feb 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/19204

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