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

Bunztman A, Vincent BG, Krovi H, Steele S, Frelinger JA - Immun Ageing (2012)

Bottom Line: Thus, a broad polyclonal response is associated with an effective anti-viral CD8+ T cell response.The identical TCRVβ sequences were found in both the tetramerhi and tetramerlo binding populations.This narrowing of the repertoire could contribute to the progressively ineffective immune response seen in aging.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ, 85724, USA. jfrelin@email.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 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 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.

No MeSH data available.


Related in: MedlinePlus

Pinwheel depiction of the VβJβ pairs used in gp33-tetramer+ cells following infection with LCMV. Naive represents the unimmunized repertoire. The distributions are derived from the same sequences described in Figure 1. The legend is not shown because it is impossible to display all 284 VJ combinations.
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Figure 4: Pinwheel depiction of the VβJβ pairs used in gp33-tetramer+ cells following infection with LCMV. Naive represents the unimmunized repertoire. The distributions are derived from the same sequences described in Figure 1. The legend is not shown because it is impossible to display all 284 VJ combinations.

Mentions: Using the specific combination of Vβ Jβ pairs, Figure 4 shows the striking narrowing of the repertoire. We show the pinwheel of the initial Vβ Jβ pairs after initial infection, but by 15 months the pattern had strikingly simplified. At 26 months post infection just four Vβ Jβ combinations represented 82% of the clones, TRVβ2-/Jβ 2-1, 25%; TRVβ29/Jβ 2-5, 22%; TRVβ13-3/Jβ 1-1, 20% and TRVβ16/Jβ 2-5 15%. In a second 26 month post infection mouse 100% of the gp33-specific T cells were TRVβ13-3/Jβ 2-7. Thus, the dominance of the TRVβ13-3 T cells varies from mouse to mouse, but the narrowing of the repertoire did not.


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

Bunztman A, Vincent BG, Krovi H, Steele S, Frelinger JA - Immun Ageing (2012)

Pinwheel depiction of the VβJβ pairs used in gp33-tetramer+ cells following infection with LCMV. Naive represents the unimmunized repertoire. The distributions are derived from the same sequences described in Figure 1. The legend is not shown because it is impossible to display all 284 VJ combinations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472190&req=5

Figure 4: Pinwheel depiction of the VβJβ pairs used in gp33-tetramer+ cells following infection with LCMV. Naive represents the unimmunized repertoire. The distributions are derived from the same sequences described in Figure 1. The legend is not shown because it is impossible to display all 284 VJ combinations.
Mentions: Using the specific combination of Vβ Jβ pairs, Figure 4 shows the striking narrowing of the repertoire. We show the pinwheel of the initial Vβ Jβ pairs after initial infection, but by 15 months the pattern had strikingly simplified. At 26 months post infection just four Vβ Jβ combinations represented 82% of the clones, TRVβ2-/Jβ 2-1, 25%; TRVβ29/Jβ 2-5, 22%; TRVβ13-3/Jβ 1-1, 20% and TRVβ16/Jβ 2-5 15%. In a second 26 month post infection mouse 100% of the gp33-specific T cells were TRVβ13-3/Jβ 2-7. Thus, the dominance of the TRVβ13-3 T cells varies from mouse to mouse, but the narrowing of the repertoire did not.

Bottom Line: Thus, a broad polyclonal response is associated with an effective anti-viral CD8+ T cell response.The identical TCRVβ sequences were found in both the tetramerhi and tetramerlo binding populations.This narrowing of the repertoire could contribute to the progressively ineffective immune response seen in aging.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ, 85724, USA. jfrelin@email.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 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 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.

No MeSH data available.


Related in: MedlinePlus