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

Achia Khatun; Moujtaba Y. Kasmani; Ryan Zander; David M. Schauder; Jeremy P. Snook; Jian Shen; Xiaopeng Wu; Robert Burns; Yi-Guang Chen; Chien-Wei Lin; Matthew A. Williams; Weiguo Cui

doi:10.1084/jem.20200650

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

Journal article

Open access

Peer reviewed

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

Achia Khatun, Moujtaba Y. Kasmani, Ryan Zander, David M. Schauder, Jeremy P. Snook, Jian Shen, Xiaopeng Wu, Robert Burns, Yi-Guang Chen, Chien-Wei Lin, …

The Journal of experimental medicine, Vol.218(3), e20200650

03/01/2021

DOI: 10.1084/jem.20200650

PMCID: PMC7676493

PMID: 33201171

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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.

Details

Title: Subtitle: Single-cell lineage mapping of a diverse virus-specific naive CD4 T cell repertoire
Creators: Achia Khatun - Medical College of Wisconsin
Moujtaba Y. Kasmani - Medical College of Wisconsin
Ryan Zander - Versiti Blood Center of Wisconsin
David M. Schauder - Medical College of Wisconsin
Jeremy P. Snook - University of Utah
Jian Shen - Medical College of Wisconsin
Xiaopeng Wu - Versiti Blood Center of Wisconsin
Robert Burns - Versiti Blood Center of Wisconsin
Yi-Guang Chen - Medical College of Wisconsin
Chien-Wei Lin - Medical College of Wisconsin
Matthew A. Williams - University of Utah
Weiguo Cui - Medical College of Wisconsin
Resource Type: Journal article
Publication Details: The Journal of experimental medicine, Vol.218(3), e20200650
DOI: 10.1084/jem.20200650
PMID: 33201171
PMCID: PMC7676493
NLM abbreviation: J Exp Med
ISSN: 0022-1007
eISSN: 1540-9538
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: AI125741, DK127526, AI153537, DK108557, DK107541, DK121747, AI137248; DOI: 10.13039/100000048, name: American Cancer Society; name: Advancing a Healthier Wisconsin; DOI: 10.13039/501100007959, name: Cancer Research Institute; DOI: 10.13039/100000057, name: National Institute of General Medical Sciences, award: T32-GM080202; DOI: 10.13039/100008980, name: Medical College of Wisconsin
Language: English
Date published: 03/01/2021
Academic Unit: Microbiology and Immunology
Record Identifier: 9984297318002771

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