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Divergent clonal differentiation trajectories establish CD8(+) memory T cell heterogeneity during acute viral infections in humans
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- Mold, Jeff E. (author)
- Karolinska Institutet
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- Modolo, Laurent (author)
- Univ Lyon 1, LBBE, UMR CNRS 5558, Villeurbanne, France.;ENS Lyon, LBMC UMR 5239 CNRS, Lyon, France.
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- Hard, Joanna (author)
- Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden.
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- Karolinska Institutet Univ Lyon 1, LBBE, UMR CNRS 5558, Villeurbanne, France;ENS Lyon, LBMC UMR 5239 CNRS, Lyon, France. (creator_code:org_t)
- Elsevier BV, 2021
- 2021
- English.
- In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 35:8
- Journal article (peer-reviewed)
Abstract
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- The CD8(+) T cell response to an antigen is composed of many T cell clones with unique T cell receptors, together forming a heterogeneous repertoire of effector and memory cells. How individual T cell clones contribute to this heterogeneity throughout immune responses remains largely unknown. In this study, we longitudinally track human CD8(+) T cell clones expanding in response to yellow fever virus (YFV) vaccination at the single-cell level. We observed a drop in clonal diversity in blood from the acute to memory phase, suggesting that clonal selection shapes the circulating memory repertoire. Clones in the memory phase display biased differentiation trajectories along a gradient from stem cell to terminally differentiated effector memory fates. In secondary responses, YFV- and influenza-specific CD8(+) T cell clones are poised to recapitulate skewed differentiation trajectories. Collectively, we show that the sum of distinct clonal phenotypes results in the multifaceted human T cell response to acute viral infections.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
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- Royal Institute of Technology
- Karolinska Institutet
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