The shaping of the T cell repertoire
The shaping of the T cell repertoire
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DOI：
10.1016/s1074-7613(01)00086-3
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发表时间：
2001-01-01
期刊：
影响因子：
32.4
通讯作者：
Benoist, C
中科院分区：
文献类型：
--
作者：
Correia-Neves, M;Waltzinger, C;Benoist, C
通过将TCRβ转基因与由单个V基因片段和两个J基因片段组成的TCRα微区相结合，我们设计了一种小鼠品系，显示出丰富但集中的Ton多样性，仅限于CDR3α。利用单细胞聚合酶链式反应和高通量测序，我们利用这个系统来仔细研究T细胞谱系的选择和进化。出现了一些引人注目的观察结果：(1)胸腺选择产生了一个非常“凹凸不平”的曲目，具有明显的过度代表序列的子集；(2)MHC I类和II类限制性TCR可以通过CDR3α中微小的单一残基变化来区分；(3)外周的稳态扩张和存活可以显著重塑选择后的谱系，可能反映了显示不同TCR的细胞对稳态提示做出反应的潜力的差异。
By combining a TCR beta transgene with a TCR alpha minilocus comprised of a single V and two J gene segments, we engineered a mouse line exhibiting ample but focused Ton diversity, restricted to CDR3 alpha. Using single-cell PCR and high-throughput sequencing, we have exploited this system to scrutinize T cell repertoire selection and evolution. Some striking observations emerged: (1)thymic selection produces a repertoire that is very "bumpy," with marked overrepresentation of a subset of sequences; (2) MHC class I- and class II-restricted TCRs can be distinguished by minute, single-residue changes in CDR3 alpha; and (3) homeostatic expansion and survival in the periphery can markedly remold the postselection repertoire, likely reflecting variability in the potential of cells displaying different TCRs to respond to homeostatic cues.