美国斯坦福大学Polly M. Fordyce团队近期取得重要工作进展，他们研究开发了一种基于珠子的高通量绘制T细胞激活序列和力依赖性的方法。这一研究成果2022年9月5日在线发表于《自然—方法学》杂志上。

研究人员提出了一种称为BATTLES（用于大规模外源性pMHC筛选的生物力学辅助T细胞触发）的技术，该技术使用生物力学力来同时启动肽和细胞的T细胞触发。BATTLES在光谱编码的珠子上展示候选pMHCs，该珠子由能够向T细胞施加剪切载荷的热响应聚合物组成，有助于探索T细胞反应的力和序列依赖性概况。BATTLES可用于探索基本的T细胞机械生物学和基于T细胞的免疫疗法。

据介绍，适应性免疫依赖于T淋巴细胞，它使用αβ T细胞受体（TCRs）来区分主要组织相容性复合物分子（pMHCs）呈递的多肽。鉴定能够诱导强烈T细胞反应的pMHCs不仅可以更深入地了解控制免疫反应的机制，而且还可以在诊断和治疗中具有广泛的应用。体内稀疏抗原性pMHC的T细胞识别依赖于生物力学。然而，体外筛选方法试潜在的pMHCs没有力的作用，而且通常在高（非生理）pMHCs密度下，因此无法预测体内有效的激动剂。

附：英文原文

Title: A bead-based method for high-throughput mapping of the sequence- and force-dependence of T cell activation

Author: Feng, Yinnian, Zhao, Xiang, White, Adam K., Garcia, K. Christopher, Fordyce, Polly M.

Issue&Volume: 2022-09-05

Abstract: Adaptive immunity relies on T lymphocytes that use αβ T cell receptors (TCRs) to discriminate among peptides presented by major histocompatibility complex molecules (pMHCs). Identifying pMHCs capable of inducing robust T cell responses will not only enable a deeper understanding of the mechanisms governing immune responses but could also have broad applications in diagnosis and treatment. T cell recognition of sparse antigenic pMHCs in vivo relies on biomechanical forces. However, in vitro screening methods test potential pMHCs without force and often at high (nonphysiological) pMHC densities and thus fail to predict potent agonists in vivo. Here, we present a technology termed BATTLES (biomechanically assisted T cell triggering for large-scale exogenous-pMHC screening) that uses biomechanical force to initiate T cell triggering for peptides and cells in parallel. BATTLES displays candidate pMHCs on spectrally encoded beads composed of a thermo-responsive polymer capable of applying shear loads to T cells, facilitating exploration of the force- and sequence-dependent landscape of T cell responses. BATTLES can be used to explore basic T cell mechanobiology and T cell-based immunotherapies.

DOI: 10.1038/s41592-022-01592-2

Source: https://www.nature.com/articles/s41592-022-01592-2