Single-cell lineage mapping of a diverse virus-specific naive CD4 T cell repertoire.
Single-cell lineage mapping of a diverse virus-specific naive CD4 T cell repertoire.
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不同病毒特异性初始CD4 T细胞库的单细胞谱系图谱。
DOI：
10.1084/jem.20200650
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发表时间：
2021-03-01
期刊：
影响因子：
--
通讯作者：
Cui W
中科院分区：
文献类型：
--
作者：
Khatun A;Kasmani MY;Zander R;Schauder DM;Snook JP;Shen J;Wu X;Burns R;Chen YG;Lin CW;Williams MA;Cui W
scRNA-seq 和 scTCR-seq 揭示，幼稚多克隆 CD4 T 细胞库可以在急性病毒感染期间分化为多个谱系，其中一些克隆表现出首选谱系选择。 TCR 基序可以部分地将克隆内在谱系偏好偏向 TFH 命运。追踪自然 TCR 库中的单个幼稚 T 细胞如何克隆扩增、分化以及针对感染做出谱系选择的方式以前是不可能的。在这里，利用单细胞测序技术通过独特的 TCR 序列识别克隆，我们能够追踪急性淋巴细胞脉络膜脑膜炎病毒 (LCMV) 感染期间单个病毒特异性 CD4 T 细胞的克隆扩增、分化轨迹和谱系定型。值得注意的是，我们发现了病毒特异性辅助 T 细胞中以前未被重视的克隆多样性和细胞异质性。有趣的是，尽管大多数初始 CD4 T 细胞在克隆水平上产生多个谱系，但约 28% 的初始细胞表现出对 Th1 或 TFH 细胞的首选谱系选择。从机制上讲，我们发现 TCR 结构，特别是 TCR α 链的 CDR3 基序，使谱系决策向 TFH 细胞命运倾斜。
The naive polyclonal CD4 T cell repertoire can differentiate into multiple lineages during acute viral infection, with some clones exhibiting a preferred lineage choice, as revealed by scRNA-seq and scTCR-seq. TCR motifs can partially skew clone-intrinsic lineage preferences toward the TFH fate. 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.
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通讯作者：
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