Research ArticleInfectious Disease

Diversification of the antigen-specific T cell receptor repertoire after varicella zoster vaccination

Science Translational Medicine  30 Mar 2016:
Vol. 8, Issue 332, pp. 332ra46
DOI: 10.1126/scitranslmed.aaf1725

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Roofing over shingles

Resolving spots isn’t the end of the story for people infected with varicella zoster virus (VZV). VZV hides in the host, causing a latent chronic infection that can reactivate as an individual ages. Now, Qi et al. look at the effect of booster vaccination in adults on the diversity and size of the T cell repertoire specific to VZV. They found that vaccination increases the diversity of the T cell response to VZV but that a single booster may not be enough to establish clonal dominance. These data support the use of repertoire analysis as a tool to analyze the success of vaccination.

Abstract

Diversity and size of the antigen-specific T cell receptor (TCR) repertoire are two critical determinants for successful control of chronic infection. Varicella zoster virus (VZV) that establishes latency during childhood can escape control mechanisms, in particular with increasing age. We examined the TCR diversity of VZV-reactive CD4 T cells in individuals older than 50 years by studying three identical twin pairs and three unrelated individuals before and after vaccination with live attenuated VZV. Although all individuals had a small number of dominant T cell clones, the breadth of the VZV-specific repertoire differed markedly. A genetic influence was seen for the sharing of individual TCR sequences from antigen-reactive cells but not for repertoire richness or the selection of dominant clones. VZV vaccination favored the expansion of infrequent VZV antigen–reactive TCRs, including those from naïve T cells with lesser boosting of dominant T cell clones. Thus, vaccination does not reinforce the in vivo selection that occurred during chronic infection but leads to a diversification of the VZV-reactive T cell repertoire. However, a single-booster immunization seems insufficient to establish new clonal dominance. Our results suggest that repertoire analysis of antigen-specific TCRs can be an important readout to assess whether a vaccination was able to generate memory cells in clonal sizes that are necessary for immune protection.

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