T cells create vast amounts of diversity in the genes that encode their T cell receptors (TCRs), which enables individual clones to recognize specific peptide-major histocompatibility complex (MHC) ligands. Here we combined sequencing of the TCR-encoding genes with assay for transposase-accessible chromatin with sequencing (ATAC-seq) analysis at the single-cell level to provide information on the TCR specificity and epigenomic state of individual T cells. By using this approach, termed transcript-indexed ATAC-seq (T-ATAC-seq), we identified epigenomic signatures in immortalized leukemic T cells, primary human T cells from healthy volunteers and primary leukemic T cells from patient samples. In peripheral blood CD4⁺ T cells from healthy individuals, we identified cis and trans regulators of naive and memory T cell states and found substantial heterogeneity in surface-marker-defined T cell populations. In patients with a leukemic form of cutaneous T cell lymphoma, T-ATAC-seq enabled identification of leukemic and nonleukemic regulatory pathways in T cells from the same individual by allowing separation of the signals that arose from the malignant clone from the background T cell noise. Thus, T-ATAC-seq is a new tool that enables analysis of epigenomic landscapes in clonal T cells and should be valuable for studies of T cell malignancy, immunity and immunotherapy.

中文翻译：

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转录物索引的ATAC-seq，可进行精确的免疫分析。

T细胞在编码其T细胞受体（TCR）的基因中产生大量多样性，这使单个克隆能够识别特定的肽-主要组织相容性复合物（MHC）配体。在这里，我们将TCR编码基因的测序与转座酶可进入染色质的测定结合起来，并在单细胞水平上进行测序（ATAC-seq）分析，以提供有关单个T细胞的TCR特异性和表观基因组状态的信息。通过使用这种称为转录物索引的ATAC-seq（T-ATAC-seq）的方法，我们在永生化的白血病T细胞，健康志愿者的原代人T细胞和患者样品的原发性T细胞中鉴定了表观基因组特征。外周血CD4 ⁺来自健康个体的T细胞，我们鉴定了幼稚和记忆T细胞状态的顺式和反式调节子，并在表面标记定义的T细胞群体中发现了明显的异质性。在患有白血病形式的皮肤T细胞淋巴瘤的患者中，T-ATAC-seq通过允许将恶性克隆产生的信号与背景T细胞噪声分离，从而能够鉴定同一个人的T细胞中的白血病和非白血病调节途径。因此，T-ATAC-seq是一种新工具，能够分析克隆T细胞中的表观基因组情况，对于研究T细胞恶性性，免疫性和免疫疗法具有重要意义。