一步鸟枪法捕获抗原特异性pmhc刺激CD8+ T细胞活化和增殖

IF 3.7 4区 医学 Q2 CELL BIOLOGY
Lili Liu , Yateng Li , Yu Song , Zhen Sun , Wenjing Li , Bin Li , Yongjie Wang , Haibo Wang , Bin Wang
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引用次数: 0

摘要

抗原肽在癌症、传染病、自身免疫和过敏的免疫监测中起着核心作用。T细胞免疫应答抗原肽的鉴定和分离是成功的个体化过继免疫细胞治疗的关键。主要方法有基因测序和生物信息学分析。通过分析鉴定和人工合成的抗原肽仍然需要抗原呈递细胞(APC)传递到T细胞。然而,高成本和漫长的过程时间限制了其在临床实践中的应用。为了克服这一问题,本研究尝试使用链亲和素Dynabeads和生物素标记抗体从细胞裂解物中直接捕获抗原肽-主要组织相容性复合体(MHC) I类(pmhc),然后将pmhc与相同组织来源的肿瘤浸润淋巴细胞(TILs)共培养。结果表明,捕获的pmhc能够富集肿瘤抗原特异性CD8+ T细胞,并能有效诱导CD8+ T细胞的增殖和细胞毒性反应。本研究提供了一种获得肿瘤抗原pmhc的新途径,该pmhc可以富集抗原特异性CD8+ T细胞,也可以作为人工APCs (aAPCs)刺激T细胞增殖和活化。值得注意的是,这些pmhc可以刺激干细胞样记忆T细胞的增殖。总之,本研究描述了一种省时、低成本的方法来分离肿瘤抗原肽MHC复合物,帮助肿瘤抗原特异性T细胞富集、活化和增殖。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
One-step shotgun approach for antigenic specific pMHCs capture stimulated CD8+ T cell activation and proliferation

Antigenic peptides play a central role in immune surveillance in cancer, infectious disease, autoimmunity, and allergy. The identification and isolation of antigenic peptides for T cell immune response are crucial for successful personalized adoptive immune cell therapy. The mainly methods includes gene sequencing and bioinformatic analysis. The antigenic peptides which identified by analysis and artificially synthesized still need antigen presenting cell (APC) to deliver to T cells. However, high costs and lengthy process times have limited its application in clinical practice. In order to overcome it, this study attempted to directly capture antigenic peptide-major histocompatibility complex (MHC) class I (pMHCs) from cell lysates using streptavidin Dynabeads and biotin-labeled antibodies, then the pMHCs was co-cultured with tumor infiltrating lymphocytes (TILs) of the same tissue origin. The results indicated that the captured pMHCs were able to enrich the tumor antigen-specific CD8+ T cells, and also effectively induce proliferation and cytotoxic responses of CD8+ T cells. This study provided a novel approach for obtaining tumor antigenic pMHCs, which could enrich antigen-specific CD8+ T cells, and could also function as artificial APCs (aAPCs) to stimulate proliferation and activation of T cells. Notably, these pMHCs can stimulate the proliferation of stem-like memory T cells. In conclusion, this study describes a time-saving and low-cost method to isolate tumour antigen peptide MHC complexs, helping tumor antigen-specific T cell enrichment, activation, and proliferation.

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来源期刊
Cellular immunology
Cellular immunology 生物-免疫学
CiteScore
8.20
自引率
2.30%
发文量
102
审稿时长
30 days
期刊介绍: Cellular Immunology publishes original investigations concerned with the immunological activities of cells in experimental or clinical situations. The scope of the journal encompasses the broad area of in vitro and in vivo studies of cellular immune responses. Purely clinical descriptive studies are not considered. Research Areas include: • Antigen receptor sites • Autoimmunity • Delayed-type hypersensitivity or cellular immunity • Immunologic deficiency states and their reconstitution • Immunologic surveillance and tumor immunity • Immunomodulation • Immunotherapy • Lymphokines and cytokines • Nonantibody immunity • Parasite immunology • Resistance to intracellular microbial and viral infection • Thymus and lymphocyte immunobiology • Transplantation immunology • Tumor immunity.
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