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

Interesting/sort of surprising that booster immunization does not lead to a new dominant clone. Really neat study in that they studied the immune repertoire pre and post vaccination in both identical twins and unrelated individuals.

Sci Transl Med. 2016 Mar 30;8(332):332ra46. doi: 10.1126/scitranslmed.aaf1725.

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

Qi Q1, Cavanagh MM1, Le Saux S1, NamKoong H1, Kim C1, Turgano E2, Liu Y3, Wang C4, Mackey S5, Swan GE6, Dekker CL5, Olshen RA7, Boyd SD4, Weyand CM1, Tian L8, Goronzy JJ9.

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.

PMID: 27030598 [PubMed – in process]

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