过继性T细胞疗法在实体瘤治疗中展现了良好的前景，成为目前肿瘤治疗领域的一大研究热点。其中，TCR-T 疗法主要通过T细胞受体（TCR）与抗原肽-主要组织相容性复合体（pMHC）的特异性识别，进而激活过继性T细胞的抗肿瘤免疫反应。因此，全面解析TCR所靶向的抗原信息有助于提高TCR-T 疗法在临床应用中的有效性及安全性。然而，高效、高通量的TCR抗原筛选技术的缺乏限制了TCR-T疗法的发展。近年来，随着高通量测序技术、质谱流式细胞技术和计算生物学的快速发展，研究人员开发了多种TCR抗原筛选技术用于解析TCR及其特异性识别的抗原信息。本文从抗原定向筛选、TCR定向筛选以及双向筛选三方面对TCR抗原筛选技术进行归纳总结，系统介绍其优缺点，展望TCR抗原筛选技术领域的发展前景，为未来抗原筛选技术的开发提供了新思路。

Adoptive T cell therapy has shown promising prospects in solid tumors and is becoming a major focus in the field of cancer therapy. TCR-T therapy relies on the specific recognition of peptide-major histocompatibility complex (pMHC) by the T cell receptor (TCR), leading to the activation of anti-tumor immune response of adoptive T cells. Therefore, a comprehensive analysis of the information of antigens targeted by TCRs is crucial for improving the efficacy and safety of TCR-T therapy in clinical applications. However, the lack of rapid and high-throughput TCR antigen screening techniques has limited the development of TCR-T therapy. In recent years, with the rapid advancement of high-throughput sequencing technologies, mass spectrometry-based flow cytometry, and computational biology, researchers have developed various TCR antigen screening techniques to decipher the antigen-targeting information of TCRs. This review summarizes TCR antigen screening methods, categorizing them into antigen-directed screening methods, TCR-directed screening methods, and bidirectional screening methods, and systematically introduces their strengths and limitations. Moreover, it delves into the prospects of TCR antigen screening development and provides new insights into the future of this area.

国家自然科学基金（No. 32270994, No. 32300764）；江苏省杰出青年基金（No. BK20211505）；中国医学科学院医学健康前沿交叉研究专项（No. 2023-I2M-QJ-019）