TCRβ repertoire of CD4+ and CD8+ T cells is distinct in richness, distribution, and CDR3 amino acid composition

TCRβ repertoire of CD4+ and CD8+ T cells is distinct in richness, distribution, and CDR3 amino acid composition
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DOI:
10.1189/jlb.6a0215-071rr
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发表时间:
2016-03-01
影响因子:
5.5
通讯作者:
Weng, Nan-ping
Weng, Nan-ping
中科院分区:
医学3区
文献类型:
--
作者:
Li, Hoi Ming;Hiroi, Toyoko;Weng, Nan-ping

文献摘要

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TCR库是识别所有潜在病原体的TCR库。两种主要类型的T细胞,CD4(+)和CD8(+),使用相同的遗传元件和过程来产生功能性TCR,它们对MHC II类和I类结合的肽的识别不同。然而,目前尚不清楚CD4(+)和CD8(+) T细胞的TCR库在多大程度上是不同的。在这里,我们报告了使用59快速扩增cDNA末端- pcr -测序方法对CD4(+)和CD8(+) T细胞的TCR β谱进行比较分析。我们发现,在每个研究对象中,CD4(+) T细胞的TCRb丰富度范围为1.2至9.8 x 10(4),平均约为CD8(+) T细胞的5倍。此外,CD4(+)(0.3%)和CD8(+) (1.3%) T细胞之间的TCR β序列几乎没有重叠。进一步的分析表明,CD4(+)和CD8(+) T细胞对CDR3中的某些氨基酸表现出明显的偏好,这一点通过支持向量机分类器进一步证实,表明CD4(+)和CD8(+) T细胞中的TCRb CDR3存在明显的可识别的差异。最后,我们确定了5-12%的独特TCR β s与不同的可变基因共享相同的CDR3。总之,我们的研究结果揭示了CD4(+)和CD8(+) T细胞之间TCRb库的独特特征,并可能用于评估T细胞免疫能力。
The TCR repertoire serves as a reservoir of TCRs for recognizing all potential pathogens. Two major types of T cells, CD4(+) and CD8(+), that use the same genetic elements and process to generate a functional TCR differ in their recognition of peptide bound to MHC class II and I, respectively. However, it is currently unclear to what extent the TCR repertoire of CD4(+) and CD8(+) T cells is different. Here, we report a comparative analysis of the TCR beta repertoires of CD4(+) and CD8(+) T cells by use of a 59 rapid amplification of cDNA ends-PCR-sequencing method. We found that TCRb richness of CD4(+) T cells ranges from 1.2 to 9.8 x 10(4) and is approximately 5 times greater, on average, than that of CD8(+) T cells in each study subject. Furthermore, there was little overlap in TCR beta sequences between CD4(+) (0.3%) and CD8(+) (1.3%) T cells. Further analysis showed that CD4(+) and CD8(+) T cells exhibited distinct preferences for certain amino acids in the CDR3, and this was confirmed further by a support vector machine classifier, suggesting that there are distinct and discernible differences between TCRb CDR3 in CD4(+) and CD8(+) T cells. Finally, we identified 5-12% of the unique TCR beta s that share an identical CDR3 with different variable genes. Together, our findings reveal the distinct features of the TCRb repertoire between CD4(+) and CD8(+) T cells and could potentially be used to evaluate the competency of T cell immunity.