美国匹兹堡大学医学院Alok V. Joglekar团队近期取得重要工作进展，他们研究开发了CD4⁺ T细胞表位的从头鉴定的新方法。相关研究成果2024年4月24日发表于《自然—方法学》杂志上。

据介绍，CD4⁺ T细胞识别II类主要组织相容性复合体（MHC-II）分子上呈递的肽抗原，以实现其功能。T细胞受体序列的显著多样性和缺乏MHC-II的抗原发现方法使得分析CD4⁺ T细胞的特异性具有挑战性。

研究人员开发了信号传导和抗原呈递双功能受体的平台，以编码呈递共价连接肽（SABR-II）的MHC-II分子，用于CD4⁺ T细胞抗原的发现。SABR-II可以向CD4⁺ T细胞呈递表位，并在识别后诱导信号传导，从而产生可读的输出。

此外，SABR-II设计在T细胞和B细胞的信号传导和部署方面是模块化的。研究人员证明了提供内源性和非连续表位的SABR-II文库可用于1型糖尿病的抗原发现。

总之，SABR-II文库提供了一种快速、灵活、可扩展和通用的方法，用于使用实验和计算方法从单细胞RNA测序数据中从头鉴定CD4⁺ T细胞的配体。

附：英文原文

Title: De novo identification of CD4+ T cell epitopes

Author: Zdinak, Paul M., Trivedi, Nishtha, Grebinoski, Stephanie, Torrey, Jessica, Martinez, Eduardo Zarate, Martinez, Salome, Hicks, Louise, Ranjan, Rashi, Makani, Venkata Krishna Kanth, Roland, Mary Melissa, Kublo, Lyubov, Arshad, Sanya, Anderson, Mark S., Vignali, Dario A. A., Joglekar, Alok V.

Issue&Volume: 2024-04-24

Abstract: CD4+ T cells recognize peptide antigens presented on class II major histocompatibility complex (MHC-II) molecules to carry out their function. The remarkable diversity of T cell receptor sequences and lack of antigen discovery approaches for MHC-II make profiling the specificities of CD4+ T cells challenging. We have expanded our platform of signaling and antigen-presenting bifunctional receptors to encode MHC-II molecules presenting covalently linked peptides (SABR-IIs) for CD4+ T cell antigen discovery. SABR-IIs can present epitopes to CD4+ T cells and induce signaling upon their recognition, allowing a readable output. Furthermore, the SABR-II design is modular in signaling and deployment to T cells and B cells. Here, we demonstrate that SABR-IIs libraries presenting endogenous and non-contiguous epitopes can be used for antigen discovery in the context of type 1 diabetes. SABR-II libraries provide a rapid, flexible, scalable and versatile approach for de novo identification of CD4+ T cell ligands from single-cell RNA sequencing data using experimental and computational approaches. SABR-IIs are engineered bifunctional receptors that enable CD4+ T cell antigen discovery.

DOI: 10.1038/s41592-024-02255-0

Source: https://www.nature.com/articles/s41592-024-02255-0