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Single-cell lineage mapping of a diverse virus-specific naive CD4 T cell repertoire. J Exp Med 2021 Mar 01;218(3)



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-85096353007 (requires institutional sign-in at Scopus site)   30 Citations


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.

Author List

Khatun A, Kasmani MY, Zander R, Schauder DM, Snook JP, Shen J, Wu X, Burns R, Chen YG, Lin CW, Williams MA, Cui W


Yi-Guang Chen PhD Professor in the Pediatrics department at Medical College of Wisconsin
Chien-Wei Lin PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Amino Acid Motifs
CD4-Positive T-Lymphocytes
Cell Lineage
Clone Cells
Lymphocyte Subsets
Lymphocytic Choriomeningitis
Lymphocytic choriomeningitis virus
Mice, Inbred C57BL
Receptors, Antigen, T-Cell
Species Specificity