美國布萊根婦女醫(yī)院Stephen J. Elledge團(tuán)隊(duì)近期取得重要工作進(jìn)展，他們研究提出了TScan-II，一種用于鑒定CD4+ T細(xì)胞表位的基因組規(guī)模平臺。相關(guān)研究成果2023年11月27日在線發(fā)表于《細(xì)胞》雜志上。
據(jù)介紹，CD4+ T細(xì)胞在協(xié)調(diào)免疫反應(yīng)和組織穩(wěn)態(tài)中發(fā)揮著重要作用。然而，由于目前無法將多肽人類白細(xì)胞抗原II類（HLA-II）復(fù)合物與其同源T細(xì)胞受體（TCR）較好的聯(lián)系起來，從而阻礙了人們對CD4+ T細(xì)胞功能和在病理中的功能理解。
研究人員介紹TScan II，一個(gè)高度敏感的基因組CD4+抗原發(fā)現(xiàn)平臺。該平臺無縫集成了合成抗原呈遞細(xì)胞中的內(nèi)源性HLA-II抗原處理機(jī)制和T細(xì)胞中的TCR信號，能夠同時(shí)篩選多種HLA和TCR。TScan II利用基因組規(guī)模的人類、病毒組和表位誘變文庫，促進(jìn)了抗原的從頭發(fā)現(xiàn)和TCR特異性的深入探索。研究人員通過鑒定癌癥活性CD4+ T細(xì)胞克隆的非經(jīng)典抗原，證明了TScan-II在基礎(chǔ)研究和轉(zhuǎn)化研究中的潛力。
此外，研究人員鑒定了兩種用于干燥病（Sj?gren’s disease）中克隆擴(kuò)增的CD4+ T細(xì)胞的抗原，它們結(jié)合不同的HLA，并在受影響唾液腺內(nèi)的HLA II陽性導(dǎo)管細(xì)胞中表達(dá)。
附：英文原文
Title: TScan-II: A genome-scale platform for the de novo identification of CD4+ T cell epitopes
Author: Mohammad H. Dezfulian, Tomasz Kula, Thomas Pranzatelli, Nolan Kamitaki, Qingda Meng, Bhuwan Khatri, Paola Perez, Qikai Xu, Aiquan Chang, Ayano C. Kohlgruber, Yumei Leng, Ananth Aditya Jupudi, Michelle L. Joachims, John A. Chiorini, Christopher J. Lessard, A. Darise Farris, Senthil K. Muthuswamy, Blake M. Warner, Stephen J. Elledge
Issue&Volume: 2023-11-27
Abstract: CD4+ T cells play fundamental roles in orchestrating immune responses and tissue homeostasis. However, our inability to associate peptide human leukocyte antigen class-II (HLA-II) complexes with their cognate T cell receptors (TCRs) in an unbiased manner has hampered our understanding of CD4+ T cell function and role in pathologies. Here, we introduce TScan-II, a highly sensitive genome-scale CD4+ antigen discovery platform. This platform seamlessly integrates the endogenous HLA-II antigen-processing machinery in synthetic antigen-presenting cells and TCR signaling in T cells, enabling the simultaneous screening of multiple HLAs and TCRs. Leveraging genome-scale human, virome, and epitope mutagenesis libraries, TScan-II facilitates de novo antigen discovery and deep exploration of TCR specificity. We demonstrate TScan-II’s potential for basic and translational research by identifying a non-canonical antigen for a cancer-reactive CD4+ T cell clone. Additionally, we identified two antigens for clonally expanded CD4+ T cells in Sjgren’s disease, which bind distinct HLAs and are expressed in HLA-II-positive ductal cells within affected salivary glands.
來源：科學(xué)網(wǎng)
原標(biāo)題：一種用于鑒定CD4+ T細(xì)胞表位的基因組規(guī)模平臺
作者：小柯
清美聯(lián)創(chuàng)秉承“四個(gè)面向”的企業(yè)哲學(xué)和價(jià)值觀——
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北京清美聯(lián)創(chuàng)干細(xì)胞科技有限公司致力于多種干細(xì)胞臨床應(yīng)用研究，人體冷凍、核輻射防治等技術(shù)研發(fā)。
目前已擁有67種不同功能的專能細(xì)胞如神經(jīng)干細(xì)胞、胰腺干細(xì)胞、卵巢干細(xì)胞、肝臟干細(xì)胞、心肌細(xì)胞、毛囊干細(xì)胞等的制備技術(shù)。
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