Show simple item record

dc.contributor.authorClark, Fransenio
dc.contributor.authorGil, Anna
dc.contributor.authorThapa, Ishwor
dc.contributor.authorAslan, Nuray
dc.contributor.authorGhersi, Dario
dc.contributor.authorSelin, Liisa K.
dc.date.accessioned2023-05-24T13:56:26Z
dc.date.available2023-05-24T13:56:26Z
dc.date.issued2023-02-24
dc.identifier.citationClark F, Gil A, Thapa I, Aslan N, Ghersi D, Selin LK. Cross-reactivity influences changes in human influenza A virus and Epstein Barr virus specific CD8 memory T cell receptor alpha and beta repertoires between young and old. Front Immunol. 2023 Feb 24;13:1011935. doi: 10.3389/fimmu.2022.1011935. PMID: 36923729; PMCID: PMC10009332.en_US
dc.identifier.eissn1664-3224
dc.identifier.doi10.3389/fimmu.2022.1011935en_US
dc.identifier.pmid36923729
dc.identifier.urihttp://hdl.handle.net/20.500.14038/52115
dc.description.abstractOlder people have difficulty controlling infection with common viruses such as influenza A virus (IAV), RNA virus which causes recurrent infections due to a high rate of genetic mutation, and Epstein Barr virus (EBV), DNA virus which persists in B cells for life in the 95% of people that become acutely infected. We questioned whether changes in epitope-specific memory CD8 T cell receptor (TCR) repertoires to these two common viruses could occur with increasing age and contribute to waning immunity. We compared CD8 memory TCR alpha and beta repertoires in two HLA-A2+ EBV- and IAV-immune donors, young (Y) and older (O) donors to three immunodominant epitopes known to be cross-reactive, IAV-M158-66 (IAV-M1), EBV-BMLF1280-288 (EBV-BM), and EBV-BRLF1109-117 (EBV-BR). We, therefore, also designed these studies to examine if TCR cross-reactivity could contribute to changes in repertoire with increasing age. TCR high throughput sequencing showed a significant difference in the pattern of TRBV usage between Y and O. However, there were many more differences in AV and AJ usage, between the age groups suggesting that changes in TCRα usage may play a greater role in evolution of the TCR repertoire emphasizing the importance of studying TRAV repertoires. With increasing age there was a preferential retention of TCR for all three epitopes with features in their complementarity-determining region (CDR3) that increased their ease of generation, and their cross-reactive potential. Young and older donors differed in the patterns of AV/AJ and BV/BJ pairings and usage of dominant CDR3 motifs specific to all three epitopes. Both young and older donors had cross-reactive responses between these 3 epitopes, which were unique and differed from the cognate responses having features that suggested they could interact with either ligand. There was an increased tendency for the classic IAV-M1 specific clone BV19-IRSS-JB2.7/AV27-CAGGGSQGNLIF-AJ42 to appear among the cross-reactive clones, suggesting that the dominance of this clone may relate to its cross-reactivity with EBV. These results suggest that although young and older donors retain classic TCR features for each epitope their repertoires are gradually changing with age, maintaining TCRs that are cross-reactive between these two common human viruses, one with recurrent infections and the other a persistent virus which frequently reactivates.en_US
dc.language.isoenen_US
dc.relation.ispartofFrontiers in Immunologyen_US
dc.relation.urlhttps://doi.org/10.3389/fimmu.2022.1011935en_US
dc.rights© 2023 Clark, Gil, Thapa, Aslan, Ghersi and Selin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.en_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectEpstein Barr virus (EBV)-BMLF1280-288 epitopeen_US
dc.subjectEpstein Barr virus (EBV)-BRLF1109-117 epitopeen_US
dc.subjectT cell receptor (TCR) repertoireen_US
dc.subjectagingen_US
dc.subjectcrossreactivityen_US
dc.subjectinfluenza A virus (IAV)-M158-66 epitopeen_US
dc.titleCross-reactivity influences changes in human influenza A virus and Epstein Barr virus specific CD8 memory T cell receptor alpha and beta repertoires between young and olden_US
dc.typeJournal Articleen_US
dc.source.journaltitleFrontiers in immunology
dc.source.volume13
dc.source.beginpage1011935
dc.source.endpage
dc.source.countrySwitzerland
dc.identifier.journalFrontiers in immunology
refterms.dateFOA2023-05-24T13:56:27Z
dc.contributor.departmentPathologyen_US


Files in this item

Thumbnail
Name:
fimmu-13-1011935.pdf
Size:
12.88Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

© 2023 Clark, Gil, Thapa, Aslan, Ghersi and
Selin. This is an open-access article
distributed under the terms of the Creative
Commons Attribution License (CC BY). The
use, distribution or reproduction in other
forums is permitted, provided the original
author(s) and the copyright owner(s) are
credited and that the original publication in
this journal is cited, in accordance with
accepted academic practice. No use,
distribution or reproduction is permitted
which does not comply with these terms.
Except where otherwise noted, this item's license is described as © 2023 Clark, Gil, Thapa, Aslan, Ghersi and Selin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.