Highly functional T-cell receptor repertoires are abundant in stem memory T cells and highly shared among individuals

Takahiko Miyama, Takakazu Kawase, Kazutaka Kitaura, Ren Chishaki, Masashi Shibata, Kumi Oshima, Hiroshi Hamana, Hiroyuki Kishi, Atsushi Muraguchi, Kiyotaka Kuzushima, Hiroh Saji, Tadasu Shin-I, Ryuji Suzuki, Tatsuo Ichinohe

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

To expand our knowledge of the ontogeny of the T-cell receptor (TCR) repertoire of antigen-specific T-cell subsets, we combined next-generation deep sequencing and single-cell multiplex clonotype analysis to evaluate the diversity and frequency of paired TCRs, their functions and whether clonotypic TCRs are shared among different individuals. Using an HLA-A∗02-restricted cytomegalovirus (CMV) pp65-derived immunogenic peptide, we found that the more dominant pp65-specific TCR clonotypes in the blood of healthy donors have higher binding affinities for the CMV peptide and arise from clonotypes that are highly shared among individuals. Interestingly, these highly shared HLA-A∗02-restricted CMV-specific TCRs were detected in a CMV-seronegative individual as well as in HLA-A∗02-negative donors albeit at lower frequency. More intriguingly, these shared TCR clonotypes were abundant in the stem memory T-cell subset, and TCR diversity of the stem memory T-cell repertoire was significantly lower than in the central memory and effector memory T-cell repertoires. These results suggest that the stem memory T-cell subset may serve as a reservoir of highly shared and highly functional memory T-cells.

Original languageEnglish
Article number3663
JournalScientific reports
Volume7
Issue number1
DOIs
Publication statusPublished - 01-12-2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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