T cells respond to threats in an antigen-specific manner using T cell receptors (TCRs) that recognize short peptide antigens presented on major histocompatibility complex (MHC) proteins. The TCR–peptide-MHC interaction mediated between a T cell and its target cell dictates its function and thereby influences its role in disease. A lack of approaches for antigen discovery has limited the fundamental understanding of the antigenic landscape of the overall T cell response. Recent advances in high-throughput sequencing, mass cytometry, microfluidics and computational biology have led to a surge in approaches to address the challenge of T cell antigen discovery. Here, we summarize the scope of this challenge, discuss in depth the recent exciting work and highlight the outstanding questions and remaining technical hurdles in this field.

T 细胞使用 T 细胞受体 (TCR) 以抗原特异性方式对威胁作出反应，T 细胞受体 (TCR) 识别主要组织相容性复合物 (MHC) 蛋白上呈递的短肽抗原。T 细胞与其靶细胞之间介导的 TCR-肽-MHC 相互作用决定了其功能，从而影响其在疾病中的作用。缺乏抗原发现方法限制了对整个 T 细胞反应的抗原格局的基本理解。高通量测序、质谱流式细胞术、微流体和计算生物学的最新进展导致解决 T 细胞抗原发现挑战的方法激增。在这里，我们总结了这一挑战的范围，深入讨论了最近令人兴奋的工作，并突出了该领域的突出问题和剩余的技术障碍。