Specificity, Privacy, and Degeneracy in the CD4 T Cell Receptor Repertoire Following Immunization.
Specificity, Privacy, and Degeneracy in the CD4 T Cell Receptor Repertoire Following Immunization.
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DOI：
10.3389/fimmu.2017.00430
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发表时间：
2017
影响因子：
7.3
通讯作者：
Chain B
中科院分区：
文献类型：
--
作者：
Sun Y;Best K;Cinelli M;Heather JM;Reich-Zeliger S;Shifrut E;Friedman N;Shawe-Taylor J;Chain B
T细胞使用大量且多样化的抗原特异性受体来识别抗原，这些受体是由不精确的体细胞基因重排的复杂过程产生的。响应于抗原/受体结合，特异性T细胞然后分裂以形成记忆和效应群体。我们应用高通量测序技术研究卵清蛋白（OVA）和佐剂免疫后T细胞受体序列的整体变化，以了解适应性免疫如何实现特异性。每只免疫的小鼠含有一组主要是私有的但相关的扩增的CDR 3 β序列。我们使用机器学习来识别共同的模式，这些模式区分了用佐剂免疫的小鼠和用佐剂免疫的小鼠。将CDR 3 β序列解构成重叠的连续氨基酸三联体的集合。这些基序的频率用于训练线性编程增强（LPBoost）算法LPBoost以在TCR库之间进行分类。LPBoost可使用存在于沿着CDR 3的限定位置沿着的三联体序列的小子集以高于80%的准确度区分两类库。结果表明，在一个高度多样化和很大程度上是私人的T细胞受体集的背景下，这种图案赋予简并抗原特异性的模型。
T cells recognize antigen using a large and diverse set of antigen-specific receptors created by a complex process of imprecise somatic cell gene rearrangements. In response to antigen-/receptor-binding-specific T cells then divide to form memory and effector populations. We apply high-throughput sequencing to investigate the global changes in T cell receptor sequences following immunization with ovalbumin (OVA) and adjuvant, to understand how adaptive immunity achieves specificity. Each immunized mouse contained a predominantly private but related set of expanded CDR3β sequences. We used machine learning to identify common patterns which distinguished repertoires from mice immunized with adjuvant with and without OVA. The CDR3β sequences were deconstructed into sets of overlapping contiguous amino acid triplets. The frequencies of these motifs were used to train the linear programming boosting (LPBoost) algorithm LPBoost to classify between TCR repertoires. LPBoost could distinguish between the two classes of repertoire with accuracies above 80%, using a small subset of triplet sequences present at defined positions along the CDR3. The results suggest a model in which such motifs confer degenerate antigen specificity in the context of a highly diverse and largely private set of T cell receptors.