Divergent clonal differentiation trajectories establish CD8+ memory T cell heterogeneity during acute viral infections in humans.

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Mold JE, Modolo L, Hård J, Zamboni M, Larsson AJM, Stenudd M, Eriksson CJ, Durif G, Ståhl PL, Borgström E, Picelli S, Reinius B, Sandberg R, Réu P, Talavera-Lopez C, Andersson B, Blom K, Sandberg JK, Picard F, Michaëlsson J, Frisén J

Cell Rep 35 (8) 109174 [2021-05-25; online 2021-05-27]

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.

Bioinformatics Support for Computational Resources [Service]

NGI Stockholm (Genomics Applications) [Service]

NGI Stockholm (Genomics Production) [Service]

National Genomics Infrastructure [Service]

PubMed 34038736

DOI 10.1016/j.celrep.2021.109174

Crossref 10.1016/j.celrep.2021.109174

pii: S2211-1247(21)00519-2