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Single-cell lineage mapping of a diverse virus-specific naive CD4 T cell repertoire.

ABSTRACT: Tracking how individual naive T cells from a natural TCR repertoire clonally expand, differentiate, and make lineage choices in response to an infection has not previously been possible. Here, using single-cell sequencing technology to identify clones by their unique TCR sequences, we were able to trace the clonal expansion, differentiation trajectory, and lineage commitment of individual virus-specific CD4 T cells during an acute lymphocytic choriomeningitis virus (LCMV) infection. Notably, we found previously unappreciated clonal diversity and cellular heterogeneity among virus-specific helper T cells. Interestingly, although most naive CD4 T cells gave rise to multiple lineages at the clonal level, ∼28% of naive cells exhibited a preferred lineage choice toward either Th1 or TFH cells. Mechanistically, we found that TCR structure, in particular the CDR3 motif of the TCR α chain, skewed lineage decisions toward the TFH cell fate.

SUBMITTER: Khatun A

PROVIDER: S-EPMC7676493 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Single-cell lineage mapping of a diverse virus-specific naïve CD4 T cell repertoire

Project description:The naïve polyclonal CD4 T cell repertoire can differentiate into multiple lineages during acute viral infection, with some T cell clones exhibiting a preferred lineage choice. TCR α CDR3 motifs can partially influence a clone-intrinsic lineage preference towards TFH fate.

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Single-cell lineage mapping of a diverse virus-specific naïve CD4 T cell repertoire

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Follicular T helper cells shape the HCV-specific CD4+ T cell repertoire after virus elimination.

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