The same self-peptide selects conventional and regulatory CD4⁺ T cells with identical antigen receptors.
The same self-peptide selects conventional and regulatory CD4⁺ T cells with identical antigen receptors.
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DOI：
10.1038/ncomms6061
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发表时间：
2014-10-01
影响因子：
16.6
通讯作者：
Ignatowicz, Leszek
中科院分区：
文献类型：
--
作者：
Wojciech, Lukasz;Ignatowicz, Alicja;Seweryn, Michal;Rempala, Grzegorz;Pabla, Simarjot Singh;McIndoe, Richard A.;Kisielow, Pawel;Ignatowicz, Leszek
T 细胞受体 (TCR) 在胸腺细胞分化为调节性 CD4+Foxp3+ 和传统 CD4−Foxp3− T 细胞谱系中的作用仍然存在争议。根据普遍观点，与后者相比，对前一谱系的承诺要求高亲和力 TCR 结合“胸腺生态位”中存在的稀有 II 类 MHC/肽复合物，这可以解释它们的 TCR 库之间的差异。在这里，我们挑战了这一观点，并表明相同的 TCR 与相同的普遍表达的 MHC/肽复合物的结合通常将胸腺细胞引导至两个 CD4+ 谱系，表明 TCR 亲和力不起指导作用，并且“胸腺生态位”中肽的限制性呈现对于选择 CD4+Foxp3+ T 细胞来说不是必需的。然而，根据未成熟胸腺细胞是否主要以低亲和力或高亲和力结合配体，调节性CD4+T细胞和常规CD4+T细胞的库相应地相似或大部分不同，这表明负选择而不是正选择将它们分开。
The role of the T cell receptor (TCR) in commitment of thymocytes to regulatory CD4+Foxp3+ and conventional CD4−Foxp3− T cell lineages remains controversial. According to the prevailing view, commitment to the former lineage, in contrast to the latter, requires that high affinity TCRs bind rare class II MHC/peptide complexes presented in “thymic niches”, which could explain differences between their TCR repertoires. Here we challenge this view and show that the binding of identical TCRs to the same ubiquitously expressed MHC/peptide complex often directs thymocytes to both CD4+ lineages, indicating that the TCR affinity does not play the instructive role, and that restricted presentation of peptides in ”thymic niches” is not necessary for selection of CD4+Foxp3+ T cells. However, depending on whether immature thymocytes bound the ligand predominantly with low or high affinity, the repertoires of regulatory and conventional CD4+ T cells were correspondingly similar or mostly different, suggesting that negative rather than positive selection sets them apart.
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影响因子：
30.5
作者：
Hsieh, CS;Zheng, Y;Rudensky, AY
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Klein, Ludger
DOI：
10.1073/pnas.1200090109
发表时间：
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