The LCMV gp33-specific memory T cell repertoire narrows with age

Persistent Link:
http://hdl.handle.net/10150/610159
Title:
The LCMV gp33-specific memory T cell repertoire narrows with age
Author:
Bunztman, Adam; Vincent, Benjamin; Krovi, Harsha; Steele, Shaun; Frelinger, Jeffrey
Affiliation:
Department of Immunobiology, University of Arizona, Tucson, AZ, 85724, USA; Departments of Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA; Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, 27599, USA
Issue Date:
2012
Publisher:
BioMed Central
Citation:
Bunztman et al. Immunity & Ageing 2012, 9:17 http://www.immunityageing.com/content/9/1/17
Journal:
Immunity & Ageing
Rights:
© 2012 Bunztman et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND:The memory response to LCMV in mice persists for months to years with only a small decrease in the number of epitope specific CD8 T cells. This long persistence is associated with resistance to lethal LCMV disease. In contrast to studies focused on the number and surface phenotype of the memory cells, relatively little attention has been paid to the diversity of TCR usage in these cells. CD8+ T cell responses with only a few clones of identical specificity are believed to be relatively ineffective, presumably due to the relative ease of virus escape. Thus, a broad polyclonal response is associated with an effective anti-viral CD8+ T cell response.RESULTS:In this paper we show that the primary CD8+ T cell response to the LCMV gp33-41 epitope is extremely diverse. Over time while the response remains robust in terms of the number of gp33-tetramer+ T cells, the diversity of the response becomes less so. Strikingly, by 26months after infection the response is dominated by a small number TCRbeta sequences. In addition, it is of note the gp33 specific CD8+ T cells sorted by high and low tetramer binding populations 15 and 22months after infection. High and low tetramer binding cells had equivalent diversity and were dominated by a small number of clones regardless of the time tested. A similar restricted distribution was seen in NP396 specific CD8+ T cells 26months after infection. The identical TCRVbeta sequences were found in both the tetramerhi and tetramerlo binding populations. Finally, we saw no evidence of public clones in the gp33-specific response. No CDR3 sequences were found in more than one mouse.CONCLUSIONS:These data show that following LCMV infection the CD8+ gp33-specific CD8 T cell response becomes highly restricted with enormous narrowing of the diversity. This narrowing of the repertoire could contribute to the progressively ineffective immune response seen in aging.
EISSN:
1742-4933
DOI:
10.1186/1742-4933-9-17
Keywords:
CD8 T cell; T cell repertoire; T cell receptor; Aging
Version:
Final published version
Additional Links:
http://www.immunityageing.com/content/9/1/17

Full metadata record

DC FieldValue Language
dc.contributor.authorBunztman, Adamen
dc.contributor.authorVincent, Benjaminen
dc.contributor.authorKrovi, Harshaen
dc.contributor.authorSteele, Shaunen
dc.contributor.authorFrelinger, Jeffreyen
dc.date.accessioned2016-05-20T08:59:58Z-
dc.date.available2016-05-20T08:59:58Z-
dc.date.issued2012en
dc.identifier.citationBunztman et al. Immunity & Ageing 2012, 9:17 http://www.immunityageing.com/content/9/1/17en
dc.identifier.doi10.1186/1742-4933-9-17en
dc.identifier.urihttp://hdl.handle.net/10150/610159-
dc.description.abstractBACKGROUND:The memory response to LCMV in mice persists for months to years with only a small decrease in the number of epitope specific CD8 T cells. This long persistence is associated with resistance to lethal LCMV disease. In contrast to studies focused on the number and surface phenotype of the memory cells, relatively little attention has been paid to the diversity of TCR usage in these cells. CD8+ T cell responses with only a few clones of identical specificity are believed to be relatively ineffective, presumably due to the relative ease of virus escape. Thus, a broad polyclonal response is associated with an effective anti-viral CD8+ T cell response.RESULTS:In this paper we show that the primary CD8+ T cell response to the LCMV gp33-41 epitope is extremely diverse. Over time while the response remains robust in terms of the number of gp33-tetramer+ T cells, the diversity of the response becomes less so. Strikingly, by 26months after infection the response is dominated by a small number TCRbeta sequences. In addition, it is of note the gp33 specific CD8+ T cells sorted by high and low tetramer binding populations 15 and 22months after infection. High and low tetramer binding cells had equivalent diversity and were dominated by a small number of clones regardless of the time tested. A similar restricted distribution was seen in NP396 specific CD8+ T cells 26months after infection. The identical TCRVbeta sequences were found in both the tetramerhi and tetramerlo binding populations. Finally, we saw no evidence of public clones in the gp33-specific response. No CDR3 sequences were found in more than one mouse.CONCLUSIONS:These data show that following LCMV infection the CD8+ gp33-specific CD8 T cell response becomes highly restricted with enormous narrowing of the diversity. This narrowing of the repertoire could contribute to the progressively ineffective immune response seen in aging.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.immunityageing.com/content/9/1/17en
dc.rights© 2012 Bunztman et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.subjectCD8 T cellen
dc.subjectT cell repertoireen
dc.subjectT cell receptoren
dc.subjectAgingen
dc.titleThe LCMV gp33-specific memory T cell repertoire narrows with ageen
dc.typeArticleen
dc.identifier.eissn1742-4933en
dc.contributor.departmentDepartment of Immunobiology, University of Arizona, Tucson, AZ, 85724, USAen
dc.contributor.departmentDepartments of Medicine, University of North Carolina, Chapel Hill, NC, 27599, USAen
dc.contributor.departmentMicrobiology and Immunology, University of North Carolina, Chapel Hill, NC, 27599, USAen
dc.identifier.journalImmunity & Ageingen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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