CN111574614A - 一种tcr富集克隆型及其获取方法与应用 - Google Patents
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Abstract
本发明涉及生物医药技术领域,具体公开了一种TCR富集克隆型及其获取方法与应用,本发明中TCR富集克隆型的氨基酸序列为CAVGGNEKLTF_CASSQGTGRSSPLHF,其能够为疫苗开发提供了特异性识别的抗原表位,因此所述TCR富集克隆型能够用于指导疫苗开发,并为疫苗开发研究提供方向和理论依据。
Description
技术领域
本发明涉及生物医药技术领域,尤其涉及一种TCR富集克隆型及其获取方法与应用。
背景技术
新型冠状病毒(2019-novel coronavirus,2019-nCoV)感染暴发流行对全球公众健康构成了严重威胁。由2019-nCoV引起的疾病被世界卫生组织(World HealthOrganization,WHO)正式命名为COVID-19(coronavirus disease2019)。COVID-19在临床上表现为肺炎、发烧、咳嗽、肌肉疼痛、疲劳、腹泻、严重时导致死亡。WHO报告显示,2019-nCoV已造成世界大流行。接种疫苗是有效预防病毒感染流行的手段,但是目前尚无新型冠状病毒疫苗(以下简称新冠疫苗)。针对公共快速传播的COVID-19病毒,目前治疗手段仍以支持护理为主,针对COVID-19的抗病毒药物、抗体、疫苗等仍在临床实验阶段,均未研发成功。大都采用与当年SARS相同的方法对症治疗,用激素压制免疫系统引发的炎症反应,但这同时也会让人体会非常脆弱,难免受到损伤。迫切需要有效的疫苗开发遏制病毒在全球爆发。
T细胞(抗原)受体(T cell receptor,TCR),TCR为所有T细胞表面的特征性标志,以非共价键与CD3结合,形成TCR—CD3复合物。TCR的作用是识别抗原。TCR是由两条不同肽链构成的异二聚体,由α、β两条肽链组成,每条肽链又可分为可变区(V区),恒定区(C区),跨膜区和胞质区等几部分;其特点是胞质区很短。TCR分子属于免疫球蛋白超家族,其抗原特异性存在于V区;V区(Vα、Vβ)又各有三个高变区CDR1、CDR2、CDR3,其中以CDR3变异最大,直接决定了TCR的抗原结合特异性。在TCR识别MHC-抗原肽复合体时,CDR1,CDR2识别和结合MHC分子抗原结合槽的侧壁,而CDR3直接与抗原肽相结合。本发明中所提供的TCR富集克隆型通过共有的CDR3可变区对特异性的识别抗原表位具有积极作用,TCR富集克隆型能够用于指导疫苗开发,并为疫苗开发研究提供方向和理论依据。
发明内容
为了克服现有技术中存在的不足,本发明提供了一种TCR富集克隆型及其获取方法与应用。
为了实现上述目的,本发明公开了一种TCR富集克隆型,其氨基酸序列为CAVGGNEKLTF_CASSQGTGRSSPLHF。
本发明还公开了上述TCR富集克隆型的获取方法,包括以下步骤:
S1、采集治愈后病毒性感染患者的外周血单个核细胞样本;
S2、对所采集的样本进行TCR/BCR V(D)J免疫组库测序分析,找到共有的CDR3可变区;
S3、对治愈后病毒性感染患者富集程度高的细胞克隆型分布进行检测,从而可获得TCR富集克隆型。
其中,所述TCR富集克隆型在效应CD4+T记忆细胞的细胞簇中富集。
本发明还公开了所述TCR富集克隆型在指导疫苗开发中的应用。
其中,所述疫苗为2019-nCoV疫苗。
有益技术效果:本发明提供了一种TCR富集克隆型及其获取方法与应用,所述TCR富集克隆型的氨基酸序列为CAVGGNEKLTF_CASSQGTGRSSPLHF,其能够通过共有CDR3可变区对特异性识别的抗原表位具有积极意义,从而能够用于指导疫苗开发,为疫苗开发研究提供方向和理论依据。
附图说明
图1是本发明中TCR富集克隆型获取方法的流程图,
图2是本发明中TCR富集克隆型所处位置及其在TCR细胞中富集程度的示意图。
具体实施方式
为了使本技术领域的人员更好地理解本发明的技术方案,下面结合附图对本发明作进一步的详细说明。
本发明提供了一种TCR富集克隆型,其氨基酸序列为CAVGGNEKLTF_CASSQGTGRSSPLHF。
如图1、图2所示,在本实施例中,上述TCR富集克隆型的获取方法具体包括以下步骤:
S1、采集治愈后病毒性感染患者的外周血单个核细胞样本;
S2、对所采集的样本进行TCR/BCRV(D)J免疫组库测序分析,找到共有的CDR3可变区;
S3、对治愈后病毒性感染患者富集程度高的细胞克隆型分布进行检测,从而可获得所述TCR富集克隆型。
本实施例中,选取四个2019-nCoV病毒性感染患者的外周血单个核细胞作为采样样本,然后对采集样本进行TCR/BCRV(D)J免疫组库测序分析,尽管没有共有的细胞克隆型,但是存在一个共有CDR3可变区,通过对病毒性感染患者富集程度高的细胞克隆型分布进行检测,获取到富集在效应CD4+T记忆细胞细胞簇中的TCR富集克隆型,因此,所述TCR富集克隆型通过共有的CDR3可变区对特异性的识别抗原表位具有积极作用。
在本实施例中,将上述TCR富集克隆型应用于指导疫苗开发,特别是应用于指导2019-nCoV疫苗开发,由于所述TCR富集克隆型通过共有的CDR3可变区对特异性的识别抗原表位具有积极作用,因此,该TCR富集克隆型能够用于指导疫苗开发,并为疫苗开发研究提供方向和理论依据。
以上对本发明所提供的一种TCR富集克隆型及其获取方法与应用进行了详细介绍。本文中应用了具体个例对本发明的原理及实施方式进行了阐述,以上实施例的说明只是用于帮助理解本发明的核心思想。应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以对本发明进行若干改进和修饰,这些改进和修饰也落入本发明权利要求的保护范围内。
Claims (5)
1.一种TCR富集克隆型,其特征在于,其氨基酸序列为CAVGGNEKLTF_CASSQGTGRSSPLHF。
2.如权利要求1所述的TCR富集克隆型的获取方法,其特征在于,所述获取方法包括以下步骤:
S1、采集治愈后病毒性感染患者的外周血单个核细胞样本;
S2、对所采集的样本进行TCR/BCR V(D)J免疫组库测序分析,找到共有的CDR3可变区;
S3、对治愈后病毒性感染患者富集程度高的细胞克隆型分布进行检测,进而可获得所述TCR富集克隆型。
3.如权利要求2所述的TCR富集克隆型的获取方法,其特征在于,所述TCR富集克隆型在效应CD4+T记忆细胞的细胞簇中富集。
4.如权利要求1所述的TCR富集克隆型或采用权利要求2或3所述的TCR富集克隆型的获取方法获取的TCR富集克隆型在指导疫苗开发中的应用。
5.如权利要求4所述的TCR富集克隆型在指导疫苗开发中的应用,其特征在于,所述疫苗为2019-nCoV疫苗。
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PCT/CN2020/105806 WO2021237932A1 (zh) | 2020-05-23 | 2020-07-30 | Tcr富集克隆型及其获取方法与应用 |
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US11732030B2 (en) | 2020-04-02 | 2023-08-22 | Regeneron Pharmaceuticals, Inc. | Anti-SARS-CoV-2-spike glycoprotein antibodies and antigen-binding fragments |
US11999777B2 (en) | 2020-06-03 | 2024-06-04 | Regeneron Pharmaceuticals, Inc. | Methods for treating or preventing SARS-CoV-2 infections and COVID-19 with anti-SARS-CoV-2 spike glycoprotein antibodies |
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US11732030B2 (en) | 2020-04-02 | 2023-08-22 | Regeneron Pharmaceuticals, Inc. | Anti-SARS-CoV-2-spike glycoprotein antibodies and antigen-binding fragments |
US11999777B2 (en) | 2020-06-03 | 2024-06-04 | Regeneron Pharmaceuticals, Inc. | Methods for treating or preventing SARS-CoV-2 infections and COVID-19 with anti-SARS-CoV-2 spike glycoprotein antibodies |
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