Yimei Jin, Takahiko Miyama, Alexandria Brown, Tomo Hayase, Xingzhi Song, Anand K Singh, Licai Huang, Ivonne I Flores, Lauren K McDaniel, Israel Glover, Taylor M Halsey, Rishika Prasad, Valerie Chapa, Saira Ahmed, Jianhua Zhang, Kunal Rai, Christine B Peterson, Gregory Lizee, Jennifer Karmouch, Eiko Hayase, Jeffrey J Molldrem, Chia-Chi Chang, Wen-Bin Tsai, Robert R Jenq
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引用次数: 0
摘要
在全基因组范围内快速鉴定 T 细胞受体(TCR)的多肽-主要组织相容性复合体靶标的工具尚未普及。我们提出了一种新的抗原筛选方法--T-synapse(Tsyn)报告系统,它包括带有 Fas 诱导 NF-κB 报告的抗原递呈细胞(APC)和带有活化 T 细胞核因子(NFAT)报告的 T 细胞。为了从 cDNA 文库中功能性地筛选目标抗原,利用双重报告活性检测了T细胞-APC 聚合体的高效相互作用,并通过流式分拣进行了富集,然后通过深度测序(Tsyn-seq)量化了抗原鉴定。当把 Tsyn-seq 应用于先前表征的特异于人类乳头瘤病毒 16 型(HPV16)E7 抗原的 TCR 时,它成功地从来自 HPV16 阳性宫颈癌细胞系的 cDNA 文库中富集出了正确的同源抗原。Tsyn-seq 提供了一种从肿瘤 cDNA 文库中快速鉴定 TCR 识别的抗原的方法。
Tsyn-Seq: a T-cell Synapse-Based Antigen Identification Platform.
Tools for genome-wide rapid identification of peptide-major histocompatibility complex targets of T-cell receptors (TCR) are not yet universally available. We present a new antigen screening method, the T-synapse (Tsyn) reporter system, which includes antigen-presenting cells (APC) with a Fas-inducible NF-κB reporter and T cells with a nuclear factor of activated T cells (NFAT) reporter. To functionally screen for target antigens from a cDNA library, productively interacting T cell-APC aggregates were detected by dual-reporter activity and enriched by flow sorting followed by antigen identification quantified by deep sequencing (Tsyn-seq). When applied to a previously characterized TCR specific for the E7 antigen derived from human papillomavirus type 16 (HPV16), Tsyn-seq successfully enriched the correct cognate antigen from a cDNA library derived from an HPV16-positive cervical cancer cell line. Tsyn-seq provides a method for rapidly identifying antigens recognized by TCRs of interest from a tumor cDNA library. See related Spotlight by Makani and Joglekar, p. 515.
期刊介绍:
Cancer Immunology Research publishes exceptional original articles showcasing significant breakthroughs across the spectrum of cancer immunology. From fundamental inquiries into host-tumor interactions to developmental therapeutics, early translational studies, and comprehensive analyses of late-stage clinical trials, the journal provides a comprehensive view of the discipline. In addition to original research, the journal features reviews and opinion pieces of broad significance, fostering cross-disciplinary collaboration within the cancer research community. Serving as a premier resource for immunology knowledge in cancer research, the journal drives deeper insights into the host-tumor relationship, potent cancer treatments, and enhanced clinical outcomes.
Key areas of interest include endogenous antitumor immunity, tumor-promoting inflammation, cancer antigens, vaccines, antibodies, cellular therapy, cytokines, immune regulation, immune suppression, immunomodulatory effects of cancer treatment, emerging technologies, and insightful clinical investigations with immunological implications.