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

Adam Bunztman, Benjamin G. Vincent, Harsha Krovi, Shaun Steele, Jeffrey A Frelinger

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 26 months after infection the response is dominated by a small number TCRβ sequences. In addition, it is of note the gp33 specific CD8 + T cells sorted by high and low tetramer binding populations 15 and 22 months 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 26 months after infection. The identical TCRVβ sequences were found in both the tetramer hi and tetramer lo 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.

Original languageEnglish (US)
Article number17
JournalImmunity and Ageing
Volume9
DOIs
StatePublished - Aug 15 2012

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Lymphocytic choriomeningitis virus
T-Lymphocytes
Clone Cells
Infection
Epitopes
Population
Viruses
Phenotype

Keywords

  • Aging
  • CD8 T cell
  • T cell receptor
  • T cell repertoire

ASJC Scopus subject areas

  • Immunology
  • Aging

Cite this

The LCMV gp33-specific memory T cell repertoire narrows with age. / Bunztman, Adam; Vincent, Benjamin G.; Krovi, Harsha; Steele, Shaun; Frelinger, Jeffrey A.

In: Immunity and Ageing, Vol. 9, 17, 15.08.2012.

Research output: Contribution to journalArticle

Bunztman, Adam ; Vincent, Benjamin G. ; Krovi, Harsha ; Steele, Shaun ; Frelinger, Jeffrey A. / The LCMV gp33-specific memory T cell repertoire narrows with age. In: Immunity and Ageing. 2012 ; Vol. 9.
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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 26 months after infection the response is dominated by a small number TCRβ sequences. In addition, it is of note the gp33 specific CD8 + T cells sorted by high and low tetramer binding populations 15 and 22 months 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 26 months after infection. The identical TCRVβ sequences were found in both the tetramer hi and tetramer lo 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.",
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